Deposition of Energy

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

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

10537-47-0

MZOPWQKISXCCTP-UHFFFAOYSA-N

Malonoben

DTXSID1042106

UBERON:0000468

UBERON multicellular organism

GO:0040007

GO growth

WIKI decreased

Ionizing Radiation Ionizing radiation can vary in energy, dose, charge, and in the spatial distributions of energy transferred to other matter (linear energy transfer per unit length or LET) (ICRU 1970). At the same dose, low and high LET both generate energy deposition events, including many higher energy events (Goodhead and Nikjoo 1989). However, they differ in the spatial distribution and upper range of intensity of energy deposited. Lower LET such as gamma rays sparsely deposit many individual excitations or small clusters of excitations of low energy (Goodhead 1988). In contrast, high LET such as alpha particles have fewer tracks but readily transfer their energy to matter and therefore deposit their energy over a much smaller area (Goodhead 1994). Consequently, alpha and other high LET particles penetrate less deeply into tissue, interactions are densely focused on a narrow track, and individual energy depositions can be large (Goodhead 1988). These different energy deposition patterns can lead to differences in radiation effects including the pattern of DNA damage.

Exposure to ionizing radiation can come from natural and industrial sources. Space and terrestrial radiation includes a range of LET particles, while diagnostic radiation methods such as X-ray imaging, mammography and CT scans use low LET X-rays. Radiation therapy can use an external beam to direct radiation on a focused tissue area, or deposit solid or liquid radioactive materials in the body that release (mostly gamma) radiation internally. External radiotherapy typically uses X-rays but is moving towards higher LET charged particles such as protons and heavy ions (Durante, Orecchia et al. 2017).

2019-05-03T12:36:36

2019-05-07T12:12:13

2,4-Dinitrophenol

2016-11-29T18:42:27

Carbonyl cyanide-p-trifluoromethoxyphenylhydrazone

2020-11-12T17:59:28

Carbonyl cyanide m-chlorophenyl hydrazone

2020-11-12T17:59:47

Pentachlorophenol

2020-11-12T17:59:12

Triclosan

2020-11-12T18:00:07

Emodin

2020-11-20T13:48:58

Malonoben

2020-11-27T14:43:47

WCS_9606

common toxicological species human

10116

NCBI rat

10090

NCBI mouse

6239

NCBI nematode

WCS_7955

common ecological species zebrafish

3702

NCBI thale-cress

3349

NCBI Scotch pine

WCS_35525

common ecological species Daphnia magna

3055

NCBI Chlamydomonas reinhardtii

WCS_6396

common ecological species common brandling worm

WCS_4472

common ecological species Lemna minor

8030

NCBI Salmo salar

WCS_90988

common ecological species fathead minnow

Deposition of Energy

Energy Deposition

Molecular

Deposition of energy refers to events where energetic subatomic particles, nuclei, or electromagnetic radiation deposit energy in the media through which they transverse. The energy may either be sufficient (e.g. ionizing radiation) or insufficient (e.g. non-ionizing radiation) to ionize atoms or molecules (Beir et al.,1999).   Ionizing radiation can cause the ejection of electrons from atoms and molecules, thereby resulting in their ionization and the breakage of chemical bonds. The energy of these subatomic particles or electromagnetic waves mostly range from 124 KeV to 5.4 MeV and is dependent on the source and type of radiation (Zyla et al., 2020). To be ionizing the incident radiation must have sufficient energy to free electrons from atomic or molecular electron orbitals. The energy deposited can induce direct and indirect ionization events and this can be via internal (injections, inhalation, or absorption of radionuclides) or external exposure from radiation fields -- this also applies to non-ionizing radiation. Direct ionization is the principal path where charged particles interact with biological structures such as DNA, proteins or membranes to cause biological damage. Photons, which are electromagnetic waves can also deposit energy to cause direct ionization. Ionization of water, which is a major constituent of tissues and organs, produces free radical and molecular species, which themselves can indirectly damage critical targets such as DNA (Beir et al., 1999; Balagamwala et al., 2013) or alter cellular processes. Given the fundamental nature of energy deposition by radioactive/unstable nuclei, nucleons or elementary particles in material, this process is universal to all biological contexts. The spatial structure of ionizing energy deposition along the resulting particle track is represented as linear energy transfer (LET) (Hall and Giaccia, 2018 UNSCEAR, 2020). High LET refers to energy mostly above 10 keV μm-1 which produces more complex, dense structural damage than low LET radiation (below 10 keV μm-1). Low-LET particles produce sparse ionization events such as photons (X- and gamma rays), as well as high-energy protons. Low LET radiation travels farther into tissue but deposits smaller amounts of energy, whereas high LET radiation, which includes heavy ions, alpha particles and high-energy neutrons, does not travel as far but deposits larger amounts of energy into tissue at the same absorbed dose. The biological effect of the deposition of energy can be modulated by varying dose and dose rate of exposure, such as acute, chronic, or fractionated exposures (Hall and Giaccia, 2018). Non-ionizing radiation is electromagnetic waves that does not have enough energy to break bonds and induce ion formation but it can cause molecules to excite and vibrate faster resulting in biological effects. Examples of non-ionizing radiation include radio waves (wavelength: 100 km-1m), microwaves (wavelength: 1m-1mm), infrared radiation (wavelength: 1mm- 1 um), visible light (wavelengths: 400-700 nm), and ultraviolet radiation of longer wavelengths such as UVB (wavelengths: 315-400nm) and UVA (wavelengths: 280-315 nm). UVC radiation (200-280 nm) is, in contrast to UVB and UVA, considered to be a type of ionizing radiation.

<table border="1" bordercolor="#ccc" cellpadding="5" cellspacing="0" style="border-collapse:collapse"> <tbody> <tr> <td style="background-color:#eeeeee; text-align:center">Radiation type</td> <td style="background-color:#eeeeee; text-align:center"> Assay Name </td> <td style="background-color:#eeeeee; text-align:center"> References </td> <td style="background-color:#eeeeee; text-align:center"> Description </td> <td style="background-color:#eeeeee; text-align:center"> OECD Approved Assay </td> </tr> <tr> <td style="text-align:center">Ionizing radiation</td> <td style="text-align:center"> Monte Carlo Simulations (Geant4) </td> <td style="text-align:center"> Douglass et al., 2013; Douglass et al. 2012; Zyla et al., 2020 </td> <td style="text-align:center"> Monte Carlo simulations are based on a computational algorithm that mathematically models the deposition of energy into materials. </td> <td style="text-align:center"> No </td> </tr> <tr> <td style="text-align:center">Ionizing radiation</td> <td style="text-align:center"> Fluorescent Nuclear Track Detector (FNTD) </td> <td style="text-align:center"> Sawakuchi, 2016; Niklas, 2013; Koaira & Konishi, 2015 </td> <td style="text-align:center"> FNTDs are biocompatible chips with crystals of aluminium oxide doped with carbon and magnesium; used in conjuction with fluorescent microscopy, these FNTDs allow for the visualization and the linear energy transfer (LET) quantification of tracks produced by the deposition of energy into a material. </td> <td style="text-align:center"> No </td> </tr> <tr> <td style="text-align:center">Ionizing radiation</td> <td style="text-align:center">Tissue equivalent proportional counter (TEPC)</td> <td style="text-align:center">Straume et al, 2015</td> <td style="text-align:center">Measure the LET spectrum and calculate the dose equivalent.</td> <td style="text-align:center">No</td> </tr> <tr> <td style="text-align:center">Ionizing radiation</td> <td style="text-align:center">alanine dosimeters/NanoDots</td> <td style="text-align:center"> Lind et al. 2019; Xie et al., 2022 </td> <td style="text-align:center"> </td> <td style="text-align:center">No</td> </tr> <tr> <td style="text-align:center">Non-ionizing radiation</td> <td style="text-align:center">UV meters or radiameters</td> <td style="text-align:center">Xie et at., 2020</td> <td style="text-align:center">UVA/UVB (irradiance intensity), UV dosimeters (accumulated irradiance over time), Spectrophoto meter (absorption of UV by a substance or material)</td> <td style="text-align:center">No</td> </tr> </tbody> </table>

Energy can be deposited into any substrate, both living and non-living; it is independent of age, taxa, sex, or life-stage. Taxonomic applicability: This MIE is not taxonomically specific.   Life stage applicability: This MIE is not life stage specific.  Sex applicability: This MIE is not sex specific.

Low Unspecific

High

All life stages

Moderate Moderate Moderate High High High Moderate High Moderate Moderate High Low Balagamwala, E. H. et al. (2013), “Introduction to radiotherapy and standard teletherapy techniques”, Dev Ophthalmol, Vol. 52, Karger, Basel, https://doi.org/10.1159/000351045  Beir, V. et al. (1999), “The Mechanistic Basis of Radon-Induced Lung Cancer”, in Health Risks of Exposure to Radon: BEIR VI, National Academy Press, Washington, D.C., https://doi.org/10.17226/5499  Douglass, M. et al. (2013), “Monte Carlo investigation of the increased radiation deposition due to gold nanoparticles using kilovoltage and megavoltage photons in a 3D randomized cell model”, Medical Physics, Vol. 40/7, American Institute of Physics, College Park, https://doi.org/10.1118/1.4808150  Douglass, M. et al. (2012), “Development of a randomized 3D cell model for Monte Carlo microdosimetry simulations.”, Medical Physics, Vol. 39/6, American Institute of Physics, College Park, https://doi.org/10.1118/1.4719963  Hall, E. J. and Giaccia, A.J. (2018), Radiobiology for the Radiologist, 8th edition, Wolters Kluwer, Philadelphia.   Kodaira, S. and Konishi, T. (2015), “Co-visualization of DNA damage and ion traversals in live mammalian cells using a fluorescent nuclear track detector.”, Journal of Radiation Research, Vol. 56/2, Oxford University Press, Oxford, https://doi.org/10.1093/jrr/rru091  Lind, O.C., D.H. Oughton and Salbu B. (2019), "The NMBU FIGARO low dose irradiation facility", International Journal of Radiation Biology, Vol. 95/1, Taylor & Francis, London, https://doi.org/10.1080/09553002.2018.1516906. Sawakuchi, G.O. and Akselrod, M.S. (2016), “Nanoscale measurements of proton tracks using fluorescent nuclear track detectors.”, Medical Physics, Vol. 43/5, American Institute of Physics, College Park, https://doi.org/10.1118/1.4947128  Straume, T. et al. (2015), “Compact Tissue-equivalent Proportional Counter for Deep Space Human Missions.”, Health physics, Vol. 109/4, Lippincott Williams & Wilkins, Philadelphia, https://doi.org/10.1097/HP.0000000000000334  Niklas, M. et al. (2013), “Engineering cell-fluorescent ion track hybrid detectors.”, Radiation Oncology, Vol. 8/104, BioMed Central, London, https://doi.org/10.1186/1748-717X-8-141  UNSCEAR (2020), Sources, effects and risks of ionizing radiation, United Nations.  Xie, Li. et al. (2022), "Ultraviolet B Modulates Gamma Radiation-Induced Stress Responses in Lemna Minor at Multiple Levels of Biological Organisation", SSRN, Elsevier, Amsterdam, http://dx.doi.org/10.2139/ssrn.4081705 . Zyla, P.A. et al. (2020), Review of particle physics: Progress of Theoretical and Experimental Physics, 2020 Edition, Oxford University Press, Oxford.      AOPWiki 2019-08-22T09:44:23

2023-08-09T15:06:01

Increase in reactive oxygen and nitrogen species (RONS)

Increase in RONS

Molecular

Reactive oxygen and nitrogen species (RONS) are highly reactive oxygen- and nitrogen-based molecules that often contain or generate free radicals. Key molecules include superoxide ([O2]•−), hydrogen peroxide (H2O2), hydroxyl radical ([OH]•), lipid peroxide (ROOH), nitric oxide ([NO]•, and peroxynitrite ([ONOO-]) (Dickinson and Chang 2011; Egea, Fabregat et al. 2017) RONS are generated in the course of cellular respiration, metabolism, cell signaling, and inflammation (Dickinson and Chang 2011; Egea, Fabregat et al. 2017). Superoxide and hydrogen peroxide are commonly produced by the mitochondrial electron transport chain and cytochrome c and by membrane bound NADPH oxidases and related molecules. Hydrogen peroxide is also made by the endoplasmic reticulum in the course of protein folding. Nitric oxide is produced at the highest levels by nitric oxide synthase in endothelial cells and phagocytes. The other species are produced by reactions with superoxide or peroxide, or by other free radicals or enzymes. RONS activity is principally local. Most reactive oxygen species (ROS) have short half-lives, ranging from nano- to milliseconds, so diffusion is limited, while reactive nitrogen species (RNS) nitric oxide or peroxynitrate can survive long enough to diffuse across membranes (Calcerrada, Peluffo et al. 2011). Consequently, local concentrations of ROS are much higher than average cellular concentrations and signaling is typically controlled by colocalization with redox buffers (Dickinson and Chang 2011; Egea, Fabregat et al. 2017). The effects of ROS and RNS are countered by cellular antioxidants, with glutathione and peroxiredoxins playing a major role (Dickinson and Chang 2011). Glutathione is slower but broad acting, while peroxiredoxins act quickly and are specific to peroxides. Peroxiredoxins are effective at low peroxide concentrations but can be deactivated at higher concentrations, suggesting the cellular response to peroxides may sometimes be non-linear. Although their existence is limited temporally and spatially, reactive oxygen species (ROS) interact with other RONS or with other nearby molecules to produce more ROS and participate in a feedback loop to amplify the ROS signal, which can increase Reactive Nitrogen Species (RNS). Both ROS and RNS also move into neighboring cells and ROS can increase intracellular RONS signaling in neighboring cells (Egea, Fabregat et al. 2017). RONS can modify a range of targets including amino acids, lipids, and nucleic acids to inactivate or alter target functionality (Calcerrada, Peluffo et al. 2011; Dickinson and Chang 2011; Go and Jones 2013; Ravanat, Breton et al. 2014; Egea, Fabregat et al. 2017). For example, phosphatases including the tumor suppressor PTEN can be reversibly deactivated by oxidation, and the movement of HDAC4 is peroxide dependent. Elevated ROS are implicated in proliferation and maintenance of stem cell population size (Dickinson and Chang 2011) and conversely in differentiation of stem cells and oncogene-induced senescence (Egea, Fabregat et al. 2017).

RONS is typically measured using fluorescent or other probes that react with RONS to change state, or by measuring the redox state of proteins or DNA (Dickinson and Chang 2011; Wang, Fang et al. 2013; Griendling, Touyz et al. 2016). Optimal methods for RONS detection have high sensitivity, selectivity, and spatiotemporal resolution to distinguish transient and localized activity, but most methods lack one or more of these parameters. Molecular probes that indicate the presence of RONS species vary in specificity and kinetics (Dickinson and Chang 2011; Wang, Fang et al. 2013; Griendling, Touyz et al. 2016). Small molecule fluorescent probes can be applied to any tissue in vitro, but cannot be finely targeted to different cellular compartments. The non-selective probe DCHF was widely used in the past, but can produce false positive signals and is no longer recommended. Newer more selective small molecule probes such as boronate-based molecules are being developed but are not yet widely used. Alternatively, fluorescent protein-based probes can be genetically engineered, expressed in vivo, and targeted to cellular compartments and specific cells. However, these probes are very sensitive to pH in the physiological range and must be carefully controlled.  EPR (electron paramagnetic resonance spectroscopy) provide the most direct and specific detection of free radicals, but requires specialized equipment. Alternative methods involve the detection of redox-dependent changes to cellular constituents such as proteins, DNA, lipids, or glutathione (Dickinson and Chang 2011; Wang, Fang et al. 2013; Griendling, Touyz et al. 2016). However, these methods cannot generally distinguish between the oxidative species behind the changes, and cannot provide good resolution for kinetics of oxidative activity. Table 1. Common methods for detecting oxidative activity <table border="1" cellpadding="0" cellspacing="0"> <tbody> <tr> <td style="height:22px; width:133px"> Target </td> <td style="height:22px; width:126px"> Name </td> <td style="height:22px; width:144px"> Method </td> <td style="height:22px; width:235px"> Strengths/Weaknesses </td> </tr> <tr> <td style="height:22px; width:133px"> Hydrogen peroxide- extracellular </td> <td style="height:22px; width:126px"> AmplexRed </td> <td style="height:22px; width:144px"> Small molecule fluorescent probes </td> <td style="height:22px; width:235px"> Can be applied to any tissue in vitro. </td> </tr> <tr> <td style="height:22px; width:133px"> Hydrogen peroxide- mitochondrial </td> <td style="height:22px; width:126px"> MitoPy1 </td> <td style="height:22px; width:144px"> Small molecule fluorescent probes </td> <td style="height:22px; width:235px"> Can be applied to any tissue in vitro. </td> </tr> <tr> <td style="height:22px; width:133px"> Hydrogen peroxide </td> <td style="height:22px; width:126px"> HyPer </td> <td style="height:22px; width:144px"> Protein-based fluorescent probes </td> <td style="height:22px; width:235px"> Sensitive, can be targeted to specific cells and compartments. Slower and pH sensitive. </td> </tr> <tr> <td style="height:22px; width:133px"> Hydrogen peroxide </td> <td style="height:22px; width:126px"> HyPer3 </td> <td style="height:22px; width:144px"> Protein-based fluorescent probes </td> <td style="height:22px; width:235px"> Rapid kinetics and larger dynamic range, can be targeted to specific cells and compartments. Sensitive to pH, less sensitive to H2O2. </td> </tr> <tr> <td style="height:22px; width:133px"> Hydrogen peroxide </td> <td style="height:22px; width:126px"> Boronate-based indicators </td> <td style="height:22px; width:144px"> Small molecule fluorescent probe </td> <td style="height:22px; width:235px"> Selective for H2O2 but can interact with peroxynitrite. </td> </tr> <tr> <td style="height:22px; width:133px"> Superoxide- intracellular </td> <td style="height:22px; width:126px"> DHE (dihydroethidium) </td> <td style="height:22px; width:144px"> Small molecule fluorescent probe </td> <td style="height:22px; width:235px"> Can be applied to any tissue in vitro, but not targeted to different compartments. </td> </tr> <tr> <td style="height:22px; width:133px"> Superoxide- intracellular </td> <td style="height:22px; width:126px"> cpYFP </td> <td style="height:22px; width:144px"> Protein-based fluorescent probes </td> <td style="height:22px; width:235px"> Reversible. Can be targeted to specific cells and compartments. </td> </tr> <tr> <td style="height:22px; width:133px"> Superoxide- mitochondrial </td> <td style="height:22px; width:126px"> MitoSox </td> <td style="height:22px; width:144px"> Small molecule fluorescent probe </td> <td style="height:22px; width:235px"> Can be applied to any tissue in vitro. </td> </tr> <tr> <td style="height:22px; width:133px"> Superoxide- mitochondrial </td> <td style="height:22px; width:126px"> mt-cpYFP </td> <td style="height:22px; width:144px"> Protein-based fluorescent probes </td> <td style="height:22px; width:235px"> Reversible. Can be targeted to specific cells and compartments. </td> </tr> <tr> <td style="height:22px; width:133px"> Superoxide- extracellular </td> <td style="height:22px; width:126px"> nitroblue tetrazolium </td> <td style="height:22px; width:144px"> Small molecule fluorescent probe </td> <td style="height:22px; width:235px"> Can be applied to any tissue in vitro. </td> </tr> <tr> <td style="height:22px; width:133px"> Superoxide- intracellular or extracelluar </td> <td style="height:22px; width:126px"> various trityl probes </td> <td style="height:22px; width:144px"> EPR </td> <td style="height:22px; width:235px"> Very specific, but requires specialized equipment, not as sensitive in tissue. </td> </tr> <tr> <td style="height:22px; width:133px"> Nitric oxide </td> <td style="height:22px; width:126px"> Fe[DETC]2 and Fe[MGD]2, </td> <td style="height:22px; width:144px"> EPR </td> <td style="height:22px; width:235px"> Very specific, but requires specialized equipment, not as sensitive in tissue. </td> </tr> <tr> <td style="height:22px; width:133px"> Nitric oxide </td> <td style="height:22px; width:126px"> DAF-FM </td> <td style="height:22px; width:144px"> Small molecule fluorescent probe </td> <td style="height:22px; width:235px"> Can be applied to any tissue in vitro, but not targeted to different compartments </td> </tr> <tr> <td style="height:22px; width:133px"> Peroxynitrite </td> <td style="height:22px; width:126px"> EMPO </td> <td style="height:22px; width:144px"> EPR </td> <td style="height:22px; width:235px"> Very specific, but requires specialized equipment, not as sensitive in tissue. </td> </tr> <tr> <td style="height:22px; width:133px"> Peroxynitrite </td> <td style="height:22px; width:126px"> Boronate-based indicators </td> <td style="height:22px; width:144px"> Small molecule fluorescent probe </td> <td style="height:22px; width:235px"> Selective for H2O2 but can interact with (is inhibited by) peroxynitrite. </td> </tr> <tr> <td style="height:22px; width:133px"> Peroxynitrite </td> <td style="height:22px; width:126px"> 8-nitroguanine (DNA) content </td> <td style="height:22px; width:144px"> HPLC-MS/MS </td> <td style="height:22px; width:235px"> Destruction of sample required for measurement. </td> </tr> <tr> <td style="height:22px; width:133px"> Non-specific oxidation </td> <td style="height:22px; width:126px"> DCHF </td> <td style="height:22px; width:144px"> Small molecule fluorescent probe </td> <td style="height:22px; width:235px"> Very non selective, and can produce false positive signals. </td> </tr> <tr> <td style="height:22px; width:133px"> Non-specific oxidation </td> <td style="height:22px; width:126px"> roGFP or FRET </td> <td style="height:22px; width:144px"> Protein-based fluorescent probes </td> <td style="height:22px; width:235px"> Slow acting. Good to look at steady state activity. </td> </tr> <tr> <td style="height:22px; width:133px"> Non-specific oxidation </td> <td style="height:22px; width:126px"> ratio of reduced to oxidized glutathione or cysteine </td> <td style="height:22px; width:144px"> Redox state detectors </td> <td style="height:22px; width:235px"> Slow acting. Good to look at steady state activity. Destruction of sample required for measurement. </td> </tr> <tr> <td style="height:22px; width:133px"> Non-specific oxidation </td> <td style="height:22px; width:126px"> 8-oxoguanine (DNA) or protein carbonyl content </td> <td style="height:22px; width:144px"> HPLC-MS/MS </td> <td style="height:22px; width:235px"> Destruction of sample required for measurement. </td> </tr> <tr> <td style="height:22px; width:133px"> Non-specific oxidation </td> <td style="height:22px; width:126px"> TBARS (thiobarbituric acid reactive substance) </td> <td style="height:22px; width:144px"> Lipid peroxidation </td> <td style="height:22px; width:235px"> Destruction of sample required for measurement. </td> </tr> </tbody> </table>

This KE is broadly applicable across species.

<a name="_ENREF_1">Calcerrada, P., G. Peluffo, et al. (2011). "Nitric oxide-derived oxidants with a focus on peroxynitrite: molecular targets, cellular responses and therapeutic implications." Curr Pharm Des 17(35): 3905-3932.</a> <a name="_ENREF_2">Dickinson, B. C. and C. J. Chang (2011). "Chemistry and biology of reactive oxygen species in signaling or stress responses." Nature chemical biology 7(8): 504-511.</a> <a name="_ENREF_3">Egea, J., I. Fabregat, et al. (2017). "European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)." Redox biology 13: 94-162.</a> <a name="_ENREF_4">Go, Y. M. and D. P. Jones (2013). "The redox proteome." J Biol Chem 288(37): 26512-26520.</a> <a name="_ENREF_5">Griendling, K. K., R. M. Touyz, et al. (2016). "Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System: A Scientific Statement From the American Heart Association." Circulation research 119(5): e39-75.</a> <a name="_ENREF_6">Ravanat, J. L., J. Breton, et al. (2014). "Radiation-mediated formation of complex damage to DNA: a chemical aspect overview." Br J Radiol 87(1035): 20130715.</a> <a name="_ENREF_7">Wang, X., H. Fang, et al. (2013). "Imaging ROS signaling in cells and animals." Journal of molecular medicine 91(8): 917-927.</a> AOPWiki 2019-05-03T14:00:04

2019-05-08T12:30:20

increase oxidation of the di-copper moiety of the hemocyanin active site

methemocyanin formation (decrease overall oxygen binding capacity)

Molecular

AOPWiki 2022-11-16T11:37:09

2022-11-16T11:37:09

Decreased, oxygen binding capacity by hemocyanin

Decrease overall oxygen binding capacity (methemocyanin formation)

Molecular

AOPWiki 2022-11-16T12:10:10

2022-11-16T12:10:10

Cognitive, sensed as hypoxic/low oxygen environment

Hemocyanin Bohr effect decrease

Organ

AOPWiki 2022-11-16T12:28:27

2022-11-16T12:28:27

Increase, hemocyanin mRNA

Tissue

AOPWiki 2022-11-16T12:32:02

2022-11-16T12:32:02

Increase, pulmonate breathing

behavioral change leading to possible reduced feeding opportunity

Individual

AOPWiki 2022-11-16T12:38:01

2022-11-16T12:38:01

Decrease, Growth

Individual

Decreased growth refers to a reduction in size and/or weight of a tissue, organ or individual organism. Growth is normally controlled by growth factors and mainly achieved through cell proliferation (Conlon 1999).

Growth can be indicated by measuring weight, length, total volume, and/or total area of a tissue, organ or individual organism.

Taxonomic applicability domain This key event is in general applicable to all eukaryotes.   Life stage applicability domain This key event is applicable to early life stages such as embryo and juvenile.   Sex applicability domain This key event is sex-unspecific.

High Unspecific

High

Embryo

High

Juvenile

Moderate Moderate Moderate High High High Moderate

Conlon I, Raff M. 1999. Size control in animal development. Cell 96:235-244. DOI: 10.1016/s0092-8674(00)80563-2.  AOPWiki 2018-05-24T15:24:11

2022-07-06T07:36:50

Decreased, Reproductive Success

Individual

AOPWiki 2016-11-29T18:41:30

2016-12-03T16:37:53

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb8a27eb490> AOPWiki 2022-03-28T07:19:51

2022-03-28T07:19:51

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb8a2720830> AOPWiki 2022-11-16T12:49:07

2022-11-16T12:49:07

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb8a27454a0> AOPWiki 2022-11-16T12:50:24

2022-11-16T12:50:24

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb8a28de4b0> AOPWiki 2022-11-16T12:51:32

2022-11-16T12:51:32

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb8a290c518> AOPWiki 2022-11-16T12:52:36

2022-11-16T12:52:36

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb8a29357b0> AOPWiki 2022-11-16T12:53:28

2022-11-16T12:53:28

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb8a29712d8> AOPWiki 2022-11-16T12:54:21

2022-11-16T12:54:21

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#<Reference::ActiveRecord_Associations_CollectionProxy:0x00005eb8a2994620> AOPWiki 2022-11-16T12:59:03

2022-11-16T12:59:03

Energy deposition from internalized Ra-226 decay lower oxygen binding capacity of hemocyanin

Energy deposition from Ra226 decay lowers oxygen binding capacity of hemocyanin

Agnes Aggy

Danielle Beaton

BY-SA

2.5

Under development

It is well documented that ionizing radiation( (eg. X-rays, gamma, photons, alpha, beta, neutrons, heavy ions) leads to energy deposition on the atoms and molecules of the substrate. Many studies, have demonstrated that the type of radiation and distance from source has an impact on the pattern of energy deposition (Alloni, et al. 2014). High linear energy transfer (LET) radiation has been associated with higher-energy deposits (Liamsuwan et al., 2014) that are more densely-packed and cause more complex effects within the particle track (Hada and Georgakilas, 2008; Okayasu, 2012ab; Lorat et al., 2015; Nikitaki et al., 2016) in comparison to low LET radiation. Parameters such as mean lineal energy, dose mean lineal energy, frequency mean specific energy and dose mean specific energy can impact track structure of the traversed energy into a medium (Friedland et al., 2017). The detection of energy deposition by ionizing radiation can be demonstrated with the use of fluorescent nuclear track detectors (FNTDs). FNTDs used in conjunction with fluorescent microscopy, are able to visualize radiation tracks produced by ionizing radiation (Niklas et al., 2013; Kodaira et al., 2015; Sawakuchi and Akselrod, 2016). In addition, these FNTD chips can quantify the LET of primary and secondary radiation tracks up to 0.47 keV/um (Sawakuchi and Akselrod, 2016). This co-visualization of the radiation tracks and the cell markers enable the mapping of the radiation trajectory to specific cellular compartments, and the identification of accrued damage (Niklas et al., 2013; Kodaira et al., 2015). There are no known chemical initiators or prototypes that can mimic the MIE.

Growth is a regulatory relevant chronic toxicity endpoint for almost all organisms. Multiple OECD test guidelines have included growth either as a main endpoint of concern, or as an additional endpoint to be considered in the toxicity assessments. Relevant test guidelines include, but not only limited to:   -Test No. 201: Freshwater Alga and Cyanobacteria, Growth Inhibition Test -Test No. 208: Terrestrial Plant Test: Seedling Emergence and Seedling Growth Test -Test No. 211: Daphnia magna Reproduction Test -Test No. 212: Fish, Short-term Toxicity Test on Embryo and Sac-Fry Stages -Test No. 215: Fish, Juvenile Growth Test -Test No. 221: Lemna sp. Growth Inhibition Test -Test No. 228: Determination of Developmental Toxicity to Dipteran Dung Flies (Scathophaga stercoraria L. (Scathophagidae), Musca autumnalis De Geer (Muscidae)) -Test No. 241: The Larval Amphibian Growth and Development Assay (LAGDA) -Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents -Test No. 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents -Test No. 416: Two-Generation Reproduction Toxicity -Test No. 422: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test -Test No. 443: Extended One-Generation Reproductive Toxicity Study -Test No. 453: Combined Chronic Toxicity/Carcinogenicity Studies

adjacent

Low

High adjacent

Low

Moderate adjacent

Low

Moderate adjacent

Not Specified

Not Specified adjacent

Not Specified

Not Specified adjacent

Not Specified

Not Specified adjacent

Not Specified

Not Specified adjacent

Not Specified

All life stages

All blue blooded species

Energy Deposition Radiolysis Oxidation of copper moieties in copper bearing proteins Connecttion levels of biological organization  -- omics  Changes in behaviour affecting growth/survival/reproductive success

<div> <table class="table table-bordered table-fullwidth"> <thead> <tr> <th>Modulating Factor (MF)</th> <th>Influence or Outcome</th> <th>KER(s) involved</th> </tr> </thead> <tbody> <tr> <td> </td> <td> </td> <td> </td> </tr> </tbody> </table> </div>

<a name="_Ref83194273"> </a> AOPWiki 2022-11-15T16:21:55

2023-09-25T16:27:13