54-36-4FJLBFSROUSIWMA-UHFFFAOYSA-NFJLBFSROUSIWMA-UHFFFAOYSA-N
Metyrapone1-Propanone, 2-methyl-1,2-di-3-pyridinyl-
1,2-Bis(3-pyridyl)-2-methyl-1-propanone
1-Propanone, 2-methyl-1,2-di-3-pyridyl-
2-Methyl-1,2-bis(3-pyridyl)-1-propanone
2-Methyl-1,2-di(β-pyridyl)-1-propanone
2-Methyl-1,2-di-3-pyridyl-1-propanone
Mepyrapone
Methapyrapone
Methbipyranone
Methopirapone
Methopyrapone
Methopyrinine
Methopyrone
metirapona
Metopiron
Metopirone
Metopyrone
Metroprione
Metyrapon
NSC 25265
DTXSID1023314164203-73-0JWBOIMRXGHLCPP-CYBMUJFWSA-NJWBOIMRXGHLCPP-CYBMUJFWSA-N
Lysodren, Mitotan, MitotaneDTXSID3042514633125-97-2NPUKDXXFDDZOKR-UHFFFAOYNA-NNPUKDXXFDDZOKR-UHFFFAOYSA-N
Etomidate1H-Imidazole-5-carboxylic acid, 1-[(1R)-1-phenylethyl]-, ethyl ester
(+)-Etomidate
1H-Imidazole-5-carboxylic acid, 1-(1-phenylethyl)-, ethyl ester, (R)-
Amidate
D-Etomidate
Etomidat
etomidato
Hypnomidate
Imidazole-5-carboxylic acid, 1-(α-methylbenzyl)-, ethyl ester, (R)-(+)-
Propiscin
Radenarcon
DTXSID502303365277-42-1XMAYWYJOQHXEEK-OZXSUGGESA-NXMAYWYJOQHXEEK-OZXSUGGESA-N
Ketoconazole, 2R,4S-
Piperazine, 1-acetyl-4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, rel-
(.+-.)-Ketoconazole
Brizoral
cis-1-Acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazole-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine
Ethanone, 1-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]-, rel-
Fungarest
Fungoral
Ketoconazol
Ketoderm
Ketoisdin
Ketozoral
Nizoral
Onofin K
Orifungal M
Panfungol
Piperazine, 1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, cis-
Piperazine,1-acetyl-4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, rel-
DTXSID702987983-46-5KZJWDPNRJALLNS-VJSFXXLFSA-NKZJWDPNRJALLNS-VJSFXXLFSA-N
beta-SitosterolStigmast-5-en-3-ol, (3β)-
(-)-β-Sitosterol
(24R)-Ethylcholest-5-en-3β-ol
(24R)-Stigmast-5-en-3β-ol
22,23-Dihydrostigmasterol
24α-Ethylcholesterol
Angelicin
Azuprostat
Betaprost
Cinchol
Cupreol
estigmast-5-en-3-β-ol
Nimbosterol
NSC 18173
NSC 49083
NSC 8096
Prostasal
Quebrachol
Rhammol
Rhamnol
Sito-Lande
Sitosterol
Sobatum
stigmast-5-en-3-β-ol
Stigmast-5-en-3β-ol
stigmast-5-ene-3-β-ol
Stigmasterol, 22,23-dihydro-
α-Dihydrofucosterol
α-Phytosterol
β-Sitosterin
β-Sitosterol
Δ5-Stigmasten-3β-ol
DTXSID502248141859-67-0IIBYAHWJQTYFKB-UHFFFAOYSA-NIIBYAHWJQTYFKB-UHFFFAOYSA-N
BezafibratePropanoic acid, 2-[4-[2-[(4-chlorobenzoyl)amino]ethyl]phenoxy]-2-methyl-
Befizal
Benzofibrate
Bezafibrat
bezafibrato
Bezalip
Bezatol
Difaterol
DTXSID302986925812-30-0HEMJJKBWTPKOJG-UHFFFAOYSA-NHEMJJKBWTPKOJG-UHFFFAOYSA-N
GemfibrozilPentanoic acid, 5-(2,5-dimethylphenoxy)-2,2-dimethyl-
2,2-Dimethyl-5-(2,5-xylyloxy)valeric acid
5-(2,5-Dimethylphenoxy)-2,2-dimethylpentanoic acid
Decrelip
gemfibrozilo
Gevilon
Lopizid
Trialmin 900
Valeric acid, 2,2-dimethyl-5-(2,5-xylyloxy)-
DTXSID0020652117-81-7BJQHLKABXJIVAM-UHFFFAOYNA-NBJQHLKABXJIVAM-UHFFFAOYSA-N
Di(2-ethylhexyl) phthalate1,2-Benzenedicarboxylic acid, bis(2-ethylhexyl) ester
DEHP
1,2-Benzedicarboxylic acid, bis(2-ethyl-hexyl) ester
1,2-Benzenedicarboxylic acid bis(2-ethylhexyl) ester
1,2-Benzenedicarboxylic acid, 1,2-bis(2-ethylhexyl) ester
1,2-Benzenedicarboxylic acid,bis(2-ethylhexylester)
Bis(2-ethylhexyl) 1,2-benzenedicarboxylate
Bis(2-ethylhexyl) o-phthalate
bis(2-ethylhexyl) phthalate
Bis(2-ethylhexyl)phthalat
Bis(2-ethylhexyl)phthalate
Bisoflex 81
Bisoflex DOP
Corflex 400
Di(2-ethylhexyl)phthalate
Di(isooctyl) phthalate
Di-2-ethylhexlphthalate
Di-2-ethylhexyl phthalate
DI-2-ETHYLHEXYL-PHTHALATE
Diacizer DOP
Diethylhexyl phthalate
Dioctylphthalate
DOF
Ergoplast FDO
Ergoplast FDO-S
ETHYLHEXYL PHTHALATE
Eviplast 80
Eviplast 81
Fleximel
Flexol DOD
Flexol DOP
ftlalato de bis(2-etilhexilo)
Garbeflex DOP-D 40
Good-rite GP 264
Hatco DOP
Jayflex DOP
Kodaflex DEHP
Kodaflex DOP
Monocizer DOP
NSC 17069
Palatinol AH
Palatinol AH-L
Phtalate de Bis (Ethyle-2-Hexyle)
Phtalate de bis(2-ethylhexyle)
PHTHALATE, BIS(2-ETHYLHEXYL)
Phthalic acid di(2-ethylhexyl) ester
Phthalic acid, bis(2-ethylhexyl) ester
PHTHALIC ACID, BIS(2-ETHYLHEXYL)ESTER
PHTHALSAEURE-BIS-(2-AETHYLHEXYL)-ESTER
Pittsburgh PX 138
Plasthall DOP
Reomol D 79P
Sansocizer DOP
Sansocizer R 8000
Sconamoll DOP
Staflex DOP
Truflex DOP
Vestinol AH
Vinycizer 80
Vinycizer 80K
Witcizer 312
DTXSID502060752315-07-8KAATUXNTWXVJKI-UHFFFAOYNA-NKAATUXNTWXVJKI-UHFFFAOYSA-N
Cypermethrin3-(2,2-Dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid, cyano (3-phenoxyphenyl)methyl ester
Zeta-cypermethrin (ECL)
Cyclopropanecarboxylic acid, 3-(2,2-dichloroethenyl)-2,2-dimethyl-, cyano(3-phenoxyphenyl)methyl ester
(RS)-alpha-Cyano-3-phenoxybenzyl (1RS)-cis-trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
(S)-α-Cyano-3-phenoxybenzyl(1RS,3RS;1RS,3SR)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-carboxylate
3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate de α-cyano-3-phenoxybenzyle
3-(2,2-diclorovinil)-2,2-dimetilciclopropanocarboxilato de α-ciano-3-fenoxibencilo
Agrometrin
Agrothrin
Almetrin
Ambush C
Ambush CY
Antiborer 3767
Asymmethrin
Barrage
Barricade
Barricade 10EC
Basathrin
Chinimix
Chinmix
Cilcord
cis-Cypermethrin
Creokhin
Cyano(3-phenoxyphenyl)methyl 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate
Cymbush
Cympa-Ti
Cymperator
Cyperco
Cyperil
Cyperkill
Demon TC
Ecofleece Sheep Dip (Non-OP)
Ectomin
Ectopor
Flytick
Hilcyperin
Kreokhin
Leptocide
Luseweilei
Neramethrin
Neramethrin EC 50
Nurse Green
Peststop B
Peststop B 5SC
Polytrin
Prevail
Prevail FT
PYR-VU-TO 2
Ralothrin
Ripcord
Ronatak
Summerin
Supercypermethrin
Supercypermethrin forte
Supermethrin
Supersect
alpha-Cyan-3-phenoxybenzyl-3-(2,2-dichlorvinyl)-2,2-dimethylcyclopropancarboxylat
alpha-cyano-3-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
alpha-Cyano-m-phenoxybenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate
DTXSID1023998298-46-4FFGPTBGBLSHEPO-UHFFFAOYSA-NFFGPTBGBLSHEPO-UHFFFAOYSA-N
CarbamazepineCarbazepine
5H-Dibenz[b,f]azepine-5-carboxamide
5-Carbamoyl-5H-dibenz[b,f]azepine
5H-Dibenzo [b,f] azepine-5-carboxamide
Amizepin
Calepsin
Carbamazepen
Carbamazepin
carbamazepina
Carbatrol
Carbelan
Finlepsin
Geigy 32883
Karbamazepin
Karbelex
Karberol
Neurotol
Neurotop
NSC 169864
Stazepine
Tegretal
Tegretol
Tegretol XR
Telesmin
Timonil
DTXSID4022731CHEBI:3413311-Keto-testosteronePCO:0000001population of organismsGO:0006702androgen biosynthetic processPCO:0000008population growth rateD005298fertility2decreasedMetyrapone2020-07-12T10:26:362020-07-12T10:26:36Lysodren, Mitotan, Mitotane2020-07-12T10:27:102020-07-12T10:27:10Etomidate2020-07-12T10:27:522020-07-12T10:27:52Ketoconazole2017-05-02T11:08:422017-05-02T11:08:42Osilodrostat(LCI699)2020-07-12T10:30:592020-07-12T10:30:59beta-Sitosterol2020-03-23T14:04:492020-03-23T14:04:49Bezafibrate2016-11-29T18:42:272016-11-29T18:42:27Gemfibrozil<p>Fibrate drug</p>
2016-11-29T18:42:272020-03-31T10:24:40Bis(2-ethylhexyl) phthalate2016-11-29T18:42:082016-11-29T18:42:08Cypermethrin2016-11-29T18:42:272016-11-29T18:42:27Carbamazepine2016-11-29T18:42:272016-11-29T18:42:2770862teleost fish30483Order carcharhiniformesWikiUser_17mammalsWikiUser_22all species10116rat10090mouseWCS_9606humanWikiUser_6fish11β-hydroxylase inhibition11β-hydroxylase inhibitionMolecular2020-07-13T04:28:592020-07-13T04:28:59Decreased, plasma 11-ketotestosterone levelDecreased, 11KTTissue<p>11-ketotestosterone (11KT; CAS 564-35-2 | DTXSID8036499) is an oxygenated steroidal androgen with a keto group at the C11 position (Pretorius et al. 2017). </p>
<p>11-ketotestosterone is a dominant androgen in teleost fish (Borg 1994). It is synthesized from testosterone using the enzymes CYP11b1 and HSD11b (Yazawa et al., 2008; Swart et al., 2013). Zebrafish studies also show that cyp17a1 and cyp11c1 knockouts have dramatically reduced levels of 11KT (Shu et al., 2020; Zhang et al., 2020)</p>
<p>11KT is also produced by other vertebrates, although the site of its biosynthesis and physiological signficance in different taxa can vary widely. In humans, 11KT is primarily synthesized in the adrenal glands (Pretorius et al. 2017; Turcu et al. 2018). </p>
<p> </p>
<p>Although mutations in the <em>mettl3</em> gene usually cause embryonic lethality, one particular mutation in non-lethal and causes significantly reduced 11KT levels in zebrafish (Xia et al., 2018)</p>
<p>11KT production can be measured in an ex vivo steroidogenesis assay using the organism's gonad after it has been exposed to a compound.</p>
<p>The concentration of 11KT can be measured in a radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). </p>
<p>Several papers show that in fish, 11KT is correlated with testosterone levels (Spanò et al., 2004; Maclatchy & Vanderkraak, 1995; Lorenzi et al., 2008). </p>
<p>Taxanomic Applicability: Most understand of 11KT comes from studies involving teleost fish as it is their dominant androgen. Some studies have measured 11KT in sharks of the order carcharhiniformes, but there is less research in this area (Manire et al., 1999; Garnier et al. 1999; Mills et al. 2010). Many mammals possess the genes necessary to produce 11KT (NCBI), but 11KT may not be as relevant when it’s not the dominant androgen.</p>
<p>Sex Applicability: Males and females use the same biological processes to produce steroids. However, sexual dimorphism in 11KT production varies between species. In humans, plasma levels of 11KT do not differ between sexes (Imamichi et al., 2016). In Zebrafish, gonad levels of 11KT are approximately two magnitudes higher in males than females (Wang & Orban, 2007). Of the 30 other fish species sampled by Lokman et al. (2002), 11KT levels are typically dramatically lower in females than in males, but a few species of the order Perciformes show no sexual dimorphism.</p>
<p>Life Stage Applicability: 11KT can be measured in fish larvae however individuals must be pooled for sufficient sample size (Hattori et al., 2009). Lokman et al. (2002) measured plasma levels of 11-KT in several species of juvenile and adult fish. 11KT levels tend to be higher in males although some fish species don’t show sexual dimorphism. Levels of 11KT in juveniles are similar to levels in females regardless of if the species shows sexual dimorphism in 11KT levels. In males, 11KT increases for spawning and decreases afterwards (Kindler et al., 1989; Páll et al., 2002). Because of it’s involvement in reproduction, 11KT levels may not be meaningful in juveniles.</p>
UBERON:0001969blood plasmaHighMaleHighFemaleModerateJuvenileHighAdult, reproductively matureModerateLarvaeHighModerateLow<p>Borg, B. (1994). Androgens in teleost fishes. <em>Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology</em>, <em>109</em>(3), 219-245.</p>
<p>Fraz, S. et al. (2018) “Gemfibrozil and carbamazepine decrease steroid production in zebrafish testes (<em>Danio rerio</em>)”, <em>Aquatic Toxicology</em>, Vol. 198, Elsevier, pp. 1-9. https://doi.org/10.1016/j.aquatox.2018.02.006 </p>
<p>Golshan, M. & S.M.H. Alvai (2019) “Androgen signaling in male fishes: Examples of anti-androgenic chemicals that cause reproductive disorders”, <em>Theriogenology</em>, Vol. 139, Elsevier, pp. 58-71. https://doi.org/10.1016/j.theriogenology.2019.07.020 </p>
<p>Hattori, R.S. et al. (2009) “Cortisol-induced masculinization: Does thermal stress affect gonadal fate in pejerrey, a teleost fish with temperature-dependent sex determination?”, <em>PLoS ONE</em>, Vol. 4(8), pp. 1-7. doi:10.1371/journal.pone.0006548</p>
<p>Imamichi, Y. et al. (2016) “11-Ketotestosterone is a major androgen produced in human gonads”, <em>The Journal of Clinical Endocrinology & Metabolism, </em>Vol. 101(10), Oxford Academic, pp. 3582-3591. https://doi.org/10.1210/jc.2016-2311</p>
<p>Kindler, P. M. et al. (1989) “Serum 11-ketotestosterone and testosterone concentrations associated with reproduction in male bluegill (<em>Lepomis macrochirus: </em>Centrarchidae)”, <em>General and Comparative Endocrinology, </em>Vol. 75(3), Elsevier, pp. 446-453. https://doi.org/10.1016/0016-6480(89)90180-9</p>
<p>Lee, G. et al. (2019) “Effects of gemfibrozil on sex hormones and reproduction related performances of <em>Oryzias latipes </em>following long-term (155 d) and short-term (21 d) exposure”, <em>Ecotoxicology and Environmental Safety, </em>Vol. 173, Elsevier, pp. 174-181. https://doi.org/10.1016/j.ecoenv.2019.02.015</p>
<p>Lokman, P.M. et al. (2002) “11-Oxygenated androgens in female teleosts: prevalence, abundance, and life history implications”, <em>General and Comparative Endocrinology, </em>Vol. 129, Academic Press, pp. 1-12. doi: 10.1016/s0016-6480(02)00562-2</p>
<p>Lorenzi, V. et al. (2008) “Diurnal patterns and sex differences in cortisol, 11-ketotestosterone, testosterone, and 17β-estradiol in the bluebanded goby (<em>Lythrypnus dalli)</em>”, <em>General and Comparative Endocrinology, </em>Vol. 155(2)., Elsevier, pp. 438-446. https://doi.org/10.1016/j.ygcen.2007.07.010</p>
<p>MacLatchy, D.L. and G.J. Vanderkraak (1995) “The phytoestrogen β-sitosterol alters the reproductive endocrine status of goldfish”, <em>Toxicology and Applied Pharmacology, </em>Vol. 134(2), Elsevier, pp. 305-312. https://doi.org/10.1006/taap.1995.1196</p>
<p>Manire, C.A., L.E. Rasmussen & T.S. Gross (1999) “Serum steroid hormones including 11-ketotestosterone, 11-ketoandrostenedione, and dihydroprogesterone in juvenile and adult bonnethead sharks, <em>Sphyrna tiburo</em>”, <em>Journal of Experimental Zoology</em>, Vol. 284(5), Wiley-Blackwell, pp. 595-603. DOI: 10.1002/(sici)1097-010x(19991001)284:5<595::aid-jez15>3.0.co </p>
<p>Páll, M. K., I. Mayer and B. Borg (2002) “Androgen and behavior in the male three-spined stickleback, <em>Gasterosteus aculeatus </em>I. – Changes in 11-ketotestosterone levels during nesting cycle”, <em>Hormones and Behavior, </em>Vol. 41(4), Elsevier, pp. 377-383. https://doi.org/10.1006/hbeh.2002.1777</p>
<p>Pretorius, E, Arlt, W & Storbeck, K-H 2016, 'A new dawn for androgens: novel lessons from 11-oxygenated C19 steroids', Molecular and Cellular Endocrinology. https://doi.org/10.1016/j.mce.2016.08.014</p>
<p>Shu, T. et al. (2020) “Zebrafish cyp17a1 knockout reveals that androgen-mediated signaling is important for male brain sex differentiation”, <em>General and Comparative Endocrinology</em>, Vol. 295. doi:10.1016/j.ygcen.2020.113490 </p>
<p>Singh, P.B. & V. Singh (2008) “Cypermethrin induced histological changes in gonadotrophic cells, liver, gonads, plasma levels of estradiol-17beta and 11-ketotestosterone, and sperm motility in <em>Heteropneustes fossilis </em>(Bloch)”, <em>Chemosphere</em>, Vol. 72(3), Elsevier, pp. 422-431. DOI: 10.1016/j.chemosphere.2008.02.026 </p>
<p>Spanó, L. et al. (2004) “Effects of atrazine on sex steroid dynamics, plasma vitellogenin concentration and gonad development in adult goldfish (<em>Carassius auratus</em>)”, <em>Aquatic Toxicology, </em>Vol. 66(4), Elsevier, pp. 369-379. https://doi.org/10.1016/j.aquatox.2003.10.009</p>
<p>Swart, A.C. et al. (2013) “11β-hydroxyandrostenedione, the product of androstenedione metabolism in the adrenal, is metabolized in LNCaP cells by 5α-reductase yielding 11β-hydroxy-5α-androstanedione”, <em>The Journal of Steroid Biochemistry and Molecular Biology, </em>Vol 138, Elsevier, pp. 132-142. https://doi.org/10.1016/j.jsbmb.2013.04.010</p>
<p>Turcu AF, Nanba AT, Auchus RJ. The Rise, Fall, and Resurrection of 11-Oxygenated Androgens in Human Physiology and Disease. Horm Res Paediatr. 2018;89(5):284-291. doi: 10.1159/000486036. Epub 2018 May 9. PMID: 29742491; PMCID: PMC6031471.</p>
<p>Velasco-Santamaría, Y.M. et al. (2011) “Bezafibrate, a lipid-lowering pharmaceutical, as a potential endocrine disruptor in male zebrafish (<em>Danio rerio</em>)”, <em>Aquatic Toxicology, </em>Vol. 105, Elsevier, pp. 107-118. doi:10.1016/j.aquatox.2011.05.018</p>
<p>Wang, X.G. and L. Orban (2007) “Anti-Müllerian hormone and 11β-hydroxylase show reciprocal expression to that of aromatase in the transforming gonad of zebrafish males”, <em>Developmental Dynamics, </em>Vol 236(5), Wiley-Liss, pp. 1329-1338. https://doi.org/10.1002/dvdy.21129</p>
<p>Xia, H. et al. (2018) “<em>Mettl3</em> mutation disrupts gamete maturation and reduced fertility in zebrafish”, <em>Genetics</em>, Vol. 208(2), Genetics Society of America, pp. 729-743. DOI: 10.1534/genetics.117.300574 </p>
<p>Yazawa, T. (2008) “Cyp11b1 is induced in the murine gonad by luteinizing hormone/human chorionic gonadotropin and involved in the production of 11-ketotestosterone, a major fish androgen: Conservation and evolution of the androgen metabolic pathway”, <em>Endocrinology, </em>Vol. 149(4), Oxford Academy, pp. 1786-1792. https://doi.org/10.1210/en.2007-1015</p>
<p>Zheng, Q. et al. (2020) “Loss of cyp11c1 causes delayed spermatogenesis due to the absence of 11-ketotestosterone", <em>Journal of Endocrinology,</em> Vol. 244(3), Bioscientifica, pp. 487-499. https://doi.org/10.1530/JOE-19-0438 </p>
2020-03-23T11:09:032022-05-24T13:51:43Decreased spermatogenesis Decreased spermatogenesis Organ2020-07-13T04:32:492021-02-09T08:36:06Cortisol and 11β-(OH) testosterone decreasedCortisol and 11β-(OH) testosterone decreasedCellular2021-02-09T08:25:502021-02-09T08:25:50Decreased plasma Cortisol levelDecreased plasma Cortisol levelTissue2021-02-09T08:27:222021-02-09T08:27:22decreased oocyte maturationdecreased oocyte maturationOrgan2021-02-09T08:32:182021-02-09T08:32:18Decrease, 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>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Ankley GT, Jensen KM, Makynen EA, Kahl MD, Korte JJ, Hornung MW, Henry TR, Denny JS, Leino RL, Wilson VS, Cardon MD, Hartig PC, Gray LE. 2003. Effects of the androgenic growth promoter 17b-trenbolone on fecundity and reproductive endocrinology of the fathead minnow. Environ. Toxicol. Chem. 22: 1350–1360.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Bookhout TA. 1994. Research and management techniques for wildlife and habitats. The Wildlife Society, Bethesda, Maryland. 740 pp.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Caswell H. 2001. Matrix Population Models. Sinauer Associates, Inc., Sunderland, MA, USA</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Cheng WY, Zhang Q, Schroeder A, Villeneuve DL, Ankley GT, Conolly R. 2016. Computational modeling of plasma vitellogenin alterations in response to aromatase inhibition in fathead minnows. Toxicol Sci 154: 78–89.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Conolly RB, Ankley GT, Cheng W-Y, Mayo ML, Miller DH, Perkins EJ, Villeneuve DL, Watanabe KH. 2017. Quantitative adverse outcome pathways and their application to predictive toxicology. Environ. Sci. Technol. 51: 4661-4672.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Etterson MA, Ankley GT. 2021. Endogenous Lifecycle Models for Chemical Risk Assessment. Environ. Sci. Technol. 55: 15596-15608. </span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Gotelli NJ, 2008. A Primer of Ecology. Sinauer Associates, Inc., Sunderland, MA, USA.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Holbech H, Kinnberg KL, Brande-Lavridsen N, Bjerregaard P, Petersen GI, Norrgren L, Orn S, Braunbeck T, Baumann L, Bomke C, Dorgerloh M, Bruns E, Ruehl-Fehlert C, Green JW, Springer TA, Gourmelon A. 2012 Comparison of zebrafish (<em>Danio rerio</em>) and fathead minnow <em>(Pimephales promelas</em>) as test species in the Fish Sexual Development Test (FSDT). Comp. Biochem. Physiol. C Toxicol. Pharmacol. 155: 407–415.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Kramer VJ, Etterson MA, Hecker M, Murphy CA, Roesijadi G, Spade DJ, Stromberg JA, Wang M, Ankley GT. </span><span style="color:black">2011. Adverse outcome pathways and risk assessment: Bridging to population level effects. Environ. Toxicol. Chem. 30, 64-76.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">McComb B, Zuckerberg B, Vesely D, Jordan C. 2021. Monitoring Animal Populations and their Habitats: A Practitioner's Guide. Pressbooks, Oregon State University, Corvallis, OR Version 1.13, 296 pp. </span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Miller DH, Villeneuve DL, Santana Rodriguez KJ, Ankley GT. 2022. A multidimensional matrix model for predicting the effect of male biased sex ratios on fish populations. Environmental Toxicology and Chemistry 41(4): 1066-1077.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Miller DH, Tietge JE, McMaster ME, Munkittrick KR, Xia X, Griesmer DA, Ankley GT. 2015. </span><span style="color:black">Linking mechanistic toxicology to population models in forecasting recovery from chemical stress: A case study from Jackfish Bay, Ontario, Canada. Environmental Toxicology and Chemistry 34(7): 1623-1633.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Miller DH, Jensen KM, Villeneuve DE, Kahl MD, Makynen EA, Durhan EJ, Ankley GT. 2007. </span><span style="color:black">Linkage of biochemical responses to population-level effects: A case study with vitellogenin in the fathead minnow (<em>Pimephales promelas</em>). Environ Toxicol Chem 26: 521–527.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Miller DH, Ankley GT. 2004. Modeling impacts on populations: Fathead minnow (<em>Pimephales promelas</em>) exposure to the endocrine disruptor 17b-trenbolone as a case study. Ecotox Environ Saf 59: 1–9.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Murphy CA, Nisbet RM, Antczak P, Garcia-Reyero N, Gergs A, Lika K, Mathews T, Muller EB, Nacci D, Peace A, Remien CH, Schultz IR, Stevenson LM, Watanabe KH. 2018. Incorporating suborganismal processes into dynamic energy budget models for ecological risk assessment. Integrated Environmental Assessment and Management 14(5): 615–624.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Murray DL, Sandercock BK (editors). 2020. Population ecology in practice. Wiley-Blackwell, Oxford UK, 448 pp.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Nisbet RM, Jusup M, Klanjscek T, Pecquerie L. 2011. Integrating dynamic energy budget (DEB) theory with traditional bioenergetic models. The Journal of Experimental Biology 215: 892-902.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Nisbet RM, Muller EB, Lika K, Kooijman SALM. 2000. </span><span style="color:black">From molecules to ecosystems through dynamic energy budgets. J Anim Ecol 69: 913–926.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Perkins EJ, Ashauer R, Burgoon L, Conolly R, Landesmann B,, Mackay C, Murphy CA, Pollesch N, Wheeler JR, Zupanic A, Scholzk S. 2019. Building and applying quantitative adverse outcome pathway models for chemical hazard and risk assessment. Environmental Toxicology and Chemistry 38(9): 1850–1865. </span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Vandermeer JH, Goldberg DE. 2003. Population ecology: first principles. Princeton University Press, Princeton NJ, 304 pp.</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Villeneuve DL, Crump D, Garcia-Reyero N, Hecker M, Hutchinson TH, LaLone CA, Landesmann B, Lattieri T, Munn S, Nepelska M, Ottinger MA, Vergauwen L, Whelan M. Adverse outcome pathway (AOP) development 1: Strategies and principles. Toxicol Sci. 2014: 142:312–320</span></span></span></li>
<li><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="color:black">Watanabe KH, Mayo M, Jensen KM, Villeneuve DL, Ankley GT, Perkins EJ. 2016. Predicting fecundity of fathead minnows (<em>Pimephales promelas</em>) exposed to endocrine‐disrupting chemicals using a MATLAB(R)‐based model of oocyte growth dynamics. PLoS One 11: e0146594.</span></span></span></li>
</ul>
2016-11-29T18:41:242023-01-03T09:09:06impaired, Fertilityimpaired, FertilityIndividual<p><strong>Biological state</strong></p>
<p>capability to produce offspring</p>
<p><strong>Biological compartments</strong></p>
<p>System</p>
<p><strong>General role in biology</strong></p>
<p>Fertility is the capacity to conceive or induce conception. Impairment of fertility represents disorders of male or female reproductive functions or capacity.</p>
<p>As a measure, fertility rate, is the number of offspring born per mating pair, individual or population.</p>
HighAdult, reproductively matureHighHighHigh2016-11-29T18:41:242016-12-02T09:21:49c8a61cb7-0316-48a3-8ba7-e0cf524d5e27044eea39-03c4-4078-9fc1-926152e1ef762021-02-09T08:40:002021-02-09T08:40:00044eea39-03c4-4078-9fc1-926152e1ef760fbf5c6c-26ed-4399-8da5-982d9936e8752021-02-09T08:41:272021-02-09T08:41:27044eea39-03c4-4078-9fc1-926152e1ef769db0dd38-ef1c-42a0-b206-5928632611322021-02-09T08:40:452021-02-09T08:40:450fbf5c6c-26ed-4399-8da5-982d9936e8751fd9ce44-4ecc-4319-80ca-e1264d73bac02020-07-21T09:54:352020-07-21T09:54:359db0dd38-ef1c-42a0-b206-5928632611326b39f756-ed1d-4774-9c80-a0d573d2109c2021-02-09T09:00:402021-02-09T09:00:401fd9ce44-4ecc-4319-80ca-e1264d73bac0b84c8d3d-f9fd-4573-bef9-73aa0f4619502020-07-13T04:42:082020-07-13T04:42:086b39f756-ed1d-4774-9c80-a0d573d2109cb84c8d3d-f9fd-4573-bef9-73aa0f4619502021-03-26T15:32:352021-03-26T15:32:35b84c8d3d-f9fd-4573-bef9-73aa0f461950ab4052b9-f1cb-447d-8b30-dc41eb3d314d2021-03-26T15:24:012021-03-26T15:24:01Inhibition of 11β-hydroxylase leading to decresed population trajectory 11β-hydroxylase inhibition, infertility in fish <p><span style="font-family:Arial,Helvetica,sans-serif"><span style="color:black"><span style="font-size:12pt">Young Jun Kim</span><span style="font-size:13.3333px">, </span></span><span style="font-size:12.0pt"><span style="color:black">Environmental Safety Group, Korea Institute of Science and Technology (KIST) Europe Forschungsgesellschaft mbH, 66123 Saarbruecken, Germany</span></span></span></p>
<p>Park Chang-Beom, Korea Institute of Toxicology JRC-APT (Joint Research Center for Alternative and Predictive Toxicology)</p>
Under development: Not open for comment. Do not citeUnder DevelopmentIncluded in OECD Work Plan1.93<div><span style="font-family:Arial,Helvetica,sans-serif"><span style="font-size:12px">This AOP links inhibition of 11β-hydroxylase to reproductive toxicity in fish. The present AOP suggests the inhibition of 11β-hydroxylase mediated adverse outcome (AO) in fishes. In teleost, cyp11c1 encodes 11β-hydroxylase, one of the critical enzymes mediating testosterone conversion to 11β-(OH) testosterone, critical for biosynthesis of 11-KT and 11-deoxycortisol to cortisol in the differentiating gonads of both sexes at the juvenile stage. Qifeng Zhang et al, 2020 showed that the 11β-hydroxylase knockout male fish showed delayed and prolonged juvenile ovary-to-testis transition and displayed defective spermatogenesis at the adult stage, significantly reduced 11-KT and cortisol levels. Male zebrafish are infertile, have smaller testis, possess very little spermatozoa volume, and exhibit defective secondary sexual characteristics (Tang H et al.2018). </span></span></div>
<p> </p>
<div>
<table align="left">
<tbody>
<tr>
<td style="vertical-align:top">
<p style="text-align:justify"><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">11β-hydroxylase is prominently expressed in the Leydig cells of the testis in teleost. </span><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif"><span style="font-family:Arial,Helvetica,sans-serif">Ribas L, et al, 2017 reported that elevated cortisol, primary glucocorticoid, during the stress response might play a role in teleost's masculinization. Cortisol has also been cross talked to be involved in reproduction and sex differentiation at a proper level for the success of spawning, oocyte maturation, and the survival of progeny in teleosts. In females, the 11β-hydroxylase knockout females showed less spawned eggs and the eggs were defective in germinal vesicle breakdown. Stress conditions or inhibition of 11β-hydroxylase activities finally decreased 11KT and cortisol in the Leydig and Sertoli cells. Taken together, the inhibitors of 11β-hydroxylase (i.e metyrapone, lysodren, eomidate and ketoconazole etc.) could result in decreased 11-KT and cortisol, subsequently, leading to impairment of spermatogenesis and oocyte maturation and ovulation. </span> </span></span></span></p>
<p style="text-align:justify"><span style="font-size:12px"><strong>Acknowledgements</strong>: This research was supported by the National Research Council of Science & Technology(NST) grant by the Korea government (MSIP) (No. CAP-17-01-KIST Europe)<span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif"> </span></span></span></p>
</td>
</tr>
</tbody>
</table>
</div>
<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>
adjacentModerateHighadjacentModerateHighadjacentModerateHighadjacentModerateModerateadjacentModerateModerateadjacentHighHighadjacentHighHighadjacentHighHighHighMixedHighAdult, reproductively matureModerate<table cellspacing="0" class="Table" style="border-collapse:collapse; border:none; margin-left:30px; width:841px">
<tbody>
<tr>
<td colspan="2" style="background-color:#aeaaaa; border-bottom:1px solid black; border-left:1px solid black; border-right:1px solid black; border-top:1px solid black; height:17px; width:695px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><strong><u><span style="font-family:"Arial",sans-serif">To do</span></u></strong></span></span></p>
</td>
<td style="background-color:#aeaaaa; border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:1px solid black; height:17px; width:147px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><strong><u><span style="font-family:"Arial",sans-serif">Expected duration</span></u></strong></span></span></p>
</td>
</tr>
<tr>
<td rowspan="2" style="border-bottom:1px solid black; border-left:1px solid black; border-right:1px solid black; border-top:none; height:16px; width:253px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">Building the AOP frame</span></span></span></p>
</td>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:16px; width:442px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">Development of KEs</span></span></span></p>
</td>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:16px; vertical-align:top; width:147px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">3 month</span></span></span></p>
</td>
</tr>
<tr>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:17px; width:442px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">Production of experimental data for in vitro/in vivo</span></span></span></p>
</td>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:17px; vertical-align:top; width:147px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">18 month</span></span></span></p>
</td>
</tr>
<tr>
<td rowspan="5" style="border-bottom:1px solid black; border-left:1px solid black; border-right:1px solid black; border-top:none; height:16px; width:253px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">Overall assessment of the AOP</span></span></span></p>
</td>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:16px; width:442px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">Biological domain of applicability</span></span></span></p>
</td>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:16px; vertical-align:top; width:147px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">3 month</span></span></span></p>
</td>
</tr>
<tr>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:17px; width:442px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">Essentiality of all KEs</span></span></span></p>
</td>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:17px; vertical-align:top; width:147px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">3 month</span></span></span></p>
</td>
</tr>
<tr>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:16px; width:442px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">Evidence supporting all KERs</span></span></span></p>
</td>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:16px; vertical-align:top; width:147px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">5 month</span></span></span></p>
</td>
</tr>
<tr>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:17px; width:442px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">Quantitative WoE considerations</span></span></span></p>
</td>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:17px; vertical-align:top; width:147px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">5 month</span></span></span></p>
</td>
</tr>
<tr>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:17px; width:442px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">Quantitative understanding for each KER</span></span></span></p>
</td>
<td style="border-bottom:1px solid black; border-left:none; border-right:1px solid black; border-top:none; height:17px; vertical-align:top; width:147px">
<p style="text-align:center"><span style="font-size:11pt"><span style="font-family:"Times New Roman",serif"><span style="font-family:"Arial",sans-serif">6 month</span></span></span></p>
</td>
</tr>
</tbody>
</table>
<p><span style="font-size:10.0pt"><span style="font-family:"Arial",sans-serif"> This AOP is designed to estimate changes in the trajectory of fishes by potential inhibitors. Decreased trajectory applicable to both sex in the fish which is a potential endpoint for endocrine disruptions by inhibition of </span></span><span style="font-size:10.0pt"><span style="font-family:"Arial",sans-serif">11β-hydroxylase</span></span><span style="font-size:10.0pt"><span style="font-family:"Arial",sans-serif">. The proposed endpoint will provide a useful high throughput risk assessment screening tool for possible chemicals. Consequently, this AOP can be applied to the prediction of VMG-eco and relevant to EDTA caused by the inhibition of </span></span><span style="font-size:10.0pt"><span style="font-family:"Arial",sans-serif">11β-hydroxylase</span></span><span style="font-size:10.0pt"><span style="font-family:"Arial",sans-serif">. </span></span></p>
HighHighHighHighModerate<ol>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Zebrafish cyp11c1 Knockout Reveals the Roles of 11-ketotestosterone and Cortisol in Sexual Development and Reproduction. Endocrinology 2020 Jun 1;161(6):bqaa048.</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Appropriate rearing density in domesticated zebrafish to avoid masculinization: links with the stress response, J Exp Biol. 2017;220(Pt 6):1056-1064</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Loss of Cyp11c1 Causes Delayed Spermatogenesis Due to the Absence of 11-ketotestosterone. J Endocrinol 2020 Mar;244(3):487-499.</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">The Onset of Spermatogenesis in Fish. Ciba Found Symp 1994;182:255-67; discussion 267-70.</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Impaired Spermatogenesis in the Japanese Eel, Anguilla Japonica: Possibility of the Existence of Factors That Regulate Entry of Germ Cells Into Meiosis. Dev Growth Differ 1997 Dec;39(6):685-91</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Zebrafish 20β-Hydroxysteroid Dehydrogenase Type 2 Is Important for Glucocorticoid Catabolism in Stress Response PLOS 2013 8 (1) e54851</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">A newly cyp11c1-GFP transgenic zebrafish model to study corticosteroidogenesis and its perturbation by endocrine active substances at early developmental stages. Conference paper</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Large-scale transcriptome sequencing reveals novel expression patterns for key sex-related genes in a sex-changing fish. Biol Sex Differ. 2015; 6: 26.</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">A Critical Role of Follicle-Stimulating Hormone (Fsh) in Mediating the Effect of Clotrimazole on Testicular Steroidogenesis in Adult Zebrafish. Toxicology 2012 Aug 16;298(1-3):30</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Maternal stress and fish reproduction: The role of cortisol revisited Fish and Fisheries November 2018, Nov, 19(6) Pages 1016-1030</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Effects of steroid hormones on in vitro oocyte maturation in white sturgeon (Acipenser transmontanus)Fish Physiology and Biochemistry<em>, 2000</em> volume 23, pages317–325</span></span></li>
<li><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">Some aspects of oocyte maturation in catfish </span></span><span style="font-size:10.0pt"><span style="font-family:"Arial",sans-serif">Journal of Steroid Biochemistry Volume 11, Issue 1, Part 3, July 1979, Pages 701-707 </span></span><strong><span style="font-size:10.0pt"><span style="font-family:"Arial",sans-serif"> </span></span></strong></li>
<li>
<p><span style="font-size:12px"><span style="font-family:Arial,Helvetica,sans-serif">The <em>in vitro</em> metabolism of cortisol by ovarian follicles of rainbow trout (<em>Oncorhynchus mykiss</em>): comparison with ovulated oocytes and pre-hatch embryos Reproduction, Pages 713–722 Volume 144: Issue 6</span></span></p>
</li>
</ol>
2020-07-12T10:16:172023-04-29T13:02:18