Increase, Reactive Oxygen Species production

51-28-5

UFBJCMHMOXMLKC-UHFFFAOYSA-N

2,4-Dinitrophenol

DNP 1,3-Dinitro-4-hydroxybenzene 1-Hydroxy-2,4-dinitrobenzene 2,4-dinitrofenol Aldifen Dinitrophenol DINITROPHENOL, 2,4- Dinofan Fenoxyl Carbon N NSC 1532 Phenol, α-dinitro- UN 1320 UN 1599 α-Dinitrophenol Phenol, 2,4-dinitro-

DTXSID0020523

10537-47-0

MZOPWQKISXCCTP-UHFFFAOYSA-N

Malonoben

DTXSID1042106

87-86-5

IZUPBVBPLAPZRR-UHFFFAOYSA-N

Pentachlorophenol

PCP Phenol, pentachloro- 1-Hydroxy-2,3,4,5,6-pentachlorobenzene 1-Hydroxypentachlorobenzene Chlorophenasic acid CHLOROPHENATE Dowicide EC 7 Dura Treet II Fungifen Grundier Arbezol Lauxtol Liroprem NSC 263497 Penchlorol Pentachlorphenol Perchlorophenol Permasan Phenol, 2,3,4,5,6-pentachloro- Pole topper Pole topper fluid Preventol P Santophen 20 Satophen UN 3155 Witophen P Woodtreat A 2,3,4,5,6-Pentachlorophenol

DTXSID7021106

3380-34-5

XEFQLINVKFYRCS-UHFFFAOYSA-N

Triclosan

5-Chloro-2-(2,4-dichlorophenoxy)phenol Phenol, 5-chloro-2-(2,4-dichlorophenoxy)- 2, 4, 4'-Trichloro-2'-hydroxydiphenylether 2,2'-Oxybis(1',5'-dichlorophenyl-5-chlorophenol) 2,4,4'-TRICHLORO-2'-HYDROXY DIPHENYLETHER 2',4',4-Trichloro-2-hydroxydiphenyl ether 2',4,4'-Trichloro-2-hydroxydiphenyl ether 2,4,4'-Trichloro-2'-hydroxydiphenyl ether 2'-Hydroxy-2,4,4'-trichlorodiphenyl ether 2-Hydroxy-2',4,4'-trichlorodiphenyl ether 3-Chloro-6-(2,4-dichlorophenoxy)phenol 4-Chloro-2-hydroxyphenyl 2,4-dichlorophenyl ether 5-Chloro-2-(2', 4'-dichlorophenoxy) phenol Aquasept Bacti-Stat soap Cansan TCH DIPHENYL ETHER, 2,4,4'-TRICHLORO-2'-HYDROXY- Irgacare MP Irgacide LP 10 Irgaguard B 1000 Irgaguard B 1325 Irgasan Irgasan CH 3565 Irgasan DP 30 Irgasan DP 300 Irgasan DP 3000 Irgasan DP 400 Irgasan PE 30 Irgasan PG 60 Microban Additive B Microban B Oletron Phenol, 5-chloro-2-(2,4-dichlorophenoxy) Phenol, 5-chloro-2-(2,4-dichlorophenoxy)-, dihydrogen phosphate Sanitized XTX Sapoderm SterZac Tinosan AM 100 Tinosan AM 110 TRICLOSAM Ultra Fresh NM 100 Ultrafresh NM-V 2 Vinyzene DP 7000 Yujiexin Zilesan UW

DTXSID5032498

518-82-1

RHMXXJGYXNZAPX-UHFFFAOYSA-N

Emodin

9,10-Anthracenedione, 1,3,8-trihydroxy-6-methyl- 1,3,8-trihidroxi-6-metilantraquinona 1,3,8-Trihydroxy-6-methyl-9,10-anthraquinone 1,3,8-Trihydroxy-6-methylanthrachinon 1,3,8-trihydroxy-6-methylanthraquinone 1,6,8-Trihydroxy-3-methylanthraquinone 3-Methyl-1,6,8-trihydroxyanthraquinone 4,5,7-Trihydroxy-2-methylanthraquinone Anthraquinone, 1,3,8-trihydroxy-6-methyl- Frangula emodin Frangulic acid NSC 408120 NSC 622947 Rheum emodin Schuttgelb

DTXSID5025231

59456-70-1

WWJFFVUVFNBJTN-UIBIZFFUSA-N

Nikkomycins

β-D-Allofuranuronic acid, 5-[[(2S,3S,4S)-2-amino-4-hydroxy-4-(5-hydroxy-2-pyridinyl)-3-methyl-1-oxobutyl]amino]-1,5-dideoxy-1-(3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinyl)-

DTXSID5058436

CHEBI:26523

CHEBI reactive oxygen species

CHEBI:15422

CHEBI ATP

GO:1903409

GO reactive oxygen species biosynthetic process

GO:0006754

GO ATP biosynthetic process

D009026

MESH mortality

WIKI increased

WIKI decreased

Ultraviolet B radiation

2017-04-15T16:04:52

Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone

2020-11-12T17:59:28

Carbonyl cyanide m-chlorophenyl hydrazone

2020-11-12T17:59:47

2,4-Dinitrophenol

2016-11-29T18:42:27

Malonoben

2020-11-27T14:43:47

Pentachlorophenol

2020-11-12T17:59:12

Triclosan

2020-11-12T18:00:07

Emodin

2020-11-20T13:48:58

Polyoxin D

2020-10-23T06:20:12

Nikkomycins

2018-05-24T15:54:09

WCS_7955

common ecological species zebrafish

WCS_9606

common toxicological species human

10116

NCBI rat

10090

NCBI mouse

7375

NCBI Lucilia cuprina

WCS_35525

common ecological species Daphnia magna

Increase, Reactive Oxygen Species production

Increase, ROS production

Molecular

CL:0000255

CL eukaryotic cell

AOPWiki 2016-11-29T18:41:23

2021-04-11T18:03:23

Decrease, Mitochondrial membrane potential

Decrease, MMP

Cellular

AOPWiki 2020-04-30T12:41:40

2020-04-30T12:41:40

Decrease, Oxidative phosphorylation

Decrease, OXPHOS

Cellular

Oxidative phosphorylation is the process in which reducing equivalents (NADH, FADH2) produced from catabolism of carbohydrates or fatty acid are further metabolised in the mitochondrial electron transport chain (ETC) to produce ATP. This is done by a set of enzymes that responsible for building a proton gradient across the inner mitochondrial membrane that allows ATP production by the ATP synthase. When this chain is interrupted (e.g. interference by ROS, dissipation of the proton gradient, loss of integrity of the mitochondrial membranes), oxidative phosphorylation is decreased and ATP production by this means is impaired. The dissipation of the proton gradient results in a loss of the highly negative mitochondrial membrane potential (MMP) and a depletion of ATP. When the ETC is blocked, a decrease in O2 consumption rate can also be observed, as O2 is consumed to pump the protons into the intermembrane space of the mitochondria.

The MMP can be studied with mitochondrial dyes (e.g. JC-1, rhodamine 123) (Sakamuru et al. 2012), extracellular lactate reflects an increase in glycolytic rate (colorimetric assay) which can compensate for the low ATP production in the mitochondria (Limonciel et al. 2011) and O2 consumption can now be finely measured using the Seahorse device from Agilent (Abe et al. 2010)

Abe, Yoshifusa et al. 2010. “Bioenergetic Characterization of Mouse Podocytes.” American Journal of Physiology. Cell Physiology 299(2):C464-76. Retrieved December 5, 2017 (http://www.ncbi.nlm.nih.gov/pubmed/20445170). Limonciel, A. et al. 2011. “Lactate Is an Ideal Non-Invasive Marker for Evaluating Temporal Alterations in Cell Stress and Toxicity in Repeat Dose Testing Regimes.” Toxicology in Vitro 25(8). Sakamuru, Srilatha et al. 2012. “Application of a Homogenous Membrane Potential Assay to Assess Mitochondrial Function.” Physiological Genomics 44(9):495–503. Retrieved December 5, 2017 (http://www.ncbi.nlm.nih.gov/pubmed/22433785). AOPWiki 2017-10-10T07:52:53

2018-12-20T10:16:31

Decrease, Adenosine triphosphate pool

Decrease, ATP pool

Cellular

Decreased adenosine triphosphate (ATP) pool describes the loss of balance between ATP synthesis and ATP consumption, leading to reduced total ATP. As a primary form of biological energy, ATP is used by many biological processes (Bonora 2012). Decrease in ATP level normally attributes to metabolic disorders in major ATP synthetic pathways, such as mitochondrial oxidative phosphorylation, fatty acid β-oxidation, glycolysis and plant photophosphorylation.

-The ATP pool in cells or tissue can be quantified using a well-established ATP bioluminescent assay (Lemasters 1978; Wibom 1990). Assay principles: ATP can react with luciferase and luciferin from firefly and the luminescence emitted from the reaction is proportional to the ATP concentration:   ATP + D-Luciferin + O2 è Oxyluciferin + AMP + PPi + CO2 + Light -ToxCast high-throughput screening bioassays, such as “NCCT_HEK293T_CellTiterGLO” and “NIS_HEK293T_CTG_Cytotoxicity” can be used to measure this KE.

Taxonomic applicability domain This key event is in general considered applicable to all eukaryotes utilizing ATP as a direct source of energy and signaling molecule.   Life stage applicability domain This key event is considered applicable to all life stages, as all developmental stages require energy supply to maintain necessary physiological processes.   Sex applicability domain This key event is considered sex-unspecific, as both males and females use ATP as an essential energy molecule.

CL:0000000

CL cell

High Unspecific

High

Embryo

High

Juvenile

Moderate

Adult, reproductively mature

High High High High

Bonora M, Patergnani S, Rimessi A, De Marchi E, Suski JM, Bononi A, Giorgi C, Marchi S, Missiroli S, Poletti F, Wieckowski MR, Pinton P. 2012. ATP synthesis and storage. Purinergic Signalling 8:343-357. DOI: 10.1007/s11302-012-9305-8. Lemasters JJ, Hackenbrock CR. 1978. [4] Firefly luciferase assay for ATP production by mitochondria. Methods in Enzymology. Vol 57. Academic Press, pp 36-50. Wibom R, Lundin A, Hultman E. 1990. A sensitive method for measuring ATP-formation in rat muscle mitochondria. Scandinavian Journal of Clinical and Laboratory Investigation 50:143-152. DOI: 10.1080/00365519009089146.  AOPWiki 2020-04-30T12:42:35

2021-06-14T13:40:17

Increase, Mortality

Individual

This key event is observed at the biological level of the individual and describes the increase of mortality of individuals upon exposure to a stressor.

The AO can be detected by observation, for example by immobilization of the respective organisms. There exist guidelines for the characterization of this AO in arthropods. For example, the OECD 202 Daphnia sp. Acute immobilization test (OECD 2004) which can also be modified depending on the effect one expects.

Taxonomic: This AO is applicable to all living organisms. Life stage: This AO is applicable to all life stages. Sex: This AO is applicable to all sexes. Chemical: Substances known to increase mortality in arthropods are of the family of pyrimidine nucleosides (e.g. polyoxin D and nikkomycin Z) (Gijswijt et al. 1979; Tellam et al. 2000; Arakawa et al. 2008).

High Unspecific

High

All life stages

High High

Arakawa T, Yukuhiro F, Noda H. 2008. Insecticidal effect of a fungicide containing polyoxin B on the larvae of Bombyx mori (Lepidoptera: Bombycidae), Mamestra brassicae, Mythimna separata, and Spodoptera litura (Lepidoptera: Noctuidae). Appl Entomol Zool. 43(2):173–181. doi:10.1303/aez.2008.173. Gijswijt MJ, Deul DH, de Jong BJ. 1979. Inhibition of chitin synthesis by benzoyl-phenylurea insecticides, III. Similarity in action in Pieris brassicae (L.) with Polyoxin D. Pestic Biochem Physiol. 12(1):87–94. doi:10.1016/0048-3575(79)90098-1. OECD. 2004. Test No. 202: Daphnia sp. Acute Immobilisation Test. OECD OECD Guidelines for the Testing of Chemicals, Section 2. [accessed 2020 Mar 3]. https://www.oecd-ilibrary.org/environment/test-no-202-daphnia-sp-acute-immobilisation-test_9789264069947-en. Tellam RL, Vuocolo T, Johnson SE, Jarmey J, Pearson RD. 2000. Insect chitin synthase. cDNA sequence, gene organization and expression. Eur J Biochem. 267(19):6025–6043. doi:10.1046/j.1432-1327.2000.01679.x. AOPWiki 2016-11-29T18:41:24

2020-10-26T05:18:16

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42e0988458> AOPWiki 2020-04-30T12:43:55

2020-04-30T12:43:55

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b43044955d0> AOPWiki 2020-04-30T12:45:03

2020-04-30T12:45:03

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b4305c7e778> AOPWiki 2020-04-30T12:44:14

2020-04-30T12:44:14

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b4300fb79d0> AOPWiki 2020-04-30T12:44:28

2020-04-30T12:44:28

Excessive reactive oxygen species production leading to mortality (2)

Excessive ROS leading to mortality (2)

Brendan Ferreri-Hanberry

You Songa, b, *, Li Xiea, b, c, YeonKyeong Leeb,d, Knut Erik Tollefsena, b, c a Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 OSLO, Norway b Centre for Environmental Radioactivity (CERAD), Norwegian University of Life Sciences (NMBU), Post box 5003, N-1432 Ås, Norway c Norwegian University of Life Sciences (NMBU), Faculty of Environmental Sciences and Natural Resource Management (MINA), Post box 5003, N-1432 Ås, Norway d Norwegian University of Life Sciences (NMBU), Faculty of Biosciences, P.O. Box 5003, N-1432 Ås, Norway

BY-SA

2.0

The Adverse Outcome is highly significant from a regulatory point of view. It is employed as regulatory endpoint in most studies assessing the toxicity of stressors.

adjacent

Low

Moderate adjacent

Low

High adjacent

Low

High non-adjacent

Low

Moderate

Not Specified Unspecific

Not Specified

All life stages

Not Specified

High

AOPWiki 2020-04-19T04:48:39

2023-09-25T16:27:02