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All sourcesNASA NTRSDOE OSTI
NASA NTRS1995

Cosmic ray LET spectra and doses on board Cosmos-2044 biosatellite

Results of the experiments on board Cosmos-2044 (Biosatellite 9) are presented. Various nuclear track detectors (NTD) (dielectric, AgCl-based, nuclear emulsions) were used to obtain the Linear Energy Transfer (LET) spectra inside and outside the satellite. The spectra from the different NTDs have proved to be in general agreement. The results of LET spectra calculations using two different models are also presented. The resultant LET distributions are used to calculate the absorbed and equivalent doses and the orbit-averaged quality factors (QF) of the cosmic rays (CR). Absorbed dose rates inside (approximately 20 g cm (exp -2) shielding) and outside (1 g cm(exp -2) the spacecraft, omitting electrons, were found to be 4.8 and 8.6 mrad d (exp -1), respectively, while the corresponding equivalent doses were 8.8 and 19.7 mrem d(exp -1). The effects of the flight parameters on the total fluence of, and on the dose from the CR particles are analyzed. Integral dose distributions of the detected particles are also determined. The LET values which separate absorbed and equivalent doses into 50% intervals are estimated. The CR-39 dielectric NTD is shown to detect 20-30% of the absorbed dose and 60-70% of the equivalent dose in the Cosmos-2044 orbit. The influence of solar activity phase on the magnitude of CR flux is discussed.

Watts, J. W., Jr.↗
NASA NTRS1992

Cosmic ray LET spectra and doses on board Cosmos-2044 biosatellite

Results of the experiments on board Cosmos-2044 (Biosatellite 9) are presented. Various nuclear track detectors (NTD) (dielectric, AgCl-based, nuclear emulsions) were used to obtain the LET spectra inside and outside the satellite. The spectra from the different NTDs have proved to be in general agreement. The results of LET spectra calculations using two different models are also presented. The resultant LET distributions are used to calculate the absorbed and equivalent doses and the orbit-averaged quality factors (QF) of the cosmic rays (CR). Absorbed dose rates inside (approximately 20 g cm-2 shielding) and outside (1 g cm-2) the spacecraft, omitting electrons, were found to be 4.8 and 8.6 mrad d-1, respectively, while the corresponding equivalent doses were 8.8 and 19.7 mrem d-1. The effects of the flight parameters on the total fluence of, and on the dose from, the CR particles are analyzed. Integral dose distributions of the detected particles are also determined. The LET values which separate absorbed and equivalent doses into 50% intervals are estimated. The CR-39 dielectric NTD is shown to detect 20-30% of the absorbed dose and 60-70% of the equivalent dose in the Cosmos-2044 orbit. The influence of solar activity phase on the magnitude of CR flux is discussed.

Non-NASA Center↗
NASA NTRS1999

The Martian Radiation Environment from Orbit and on the Surface

A good knowledge of the Martian radiation environment and its interactions with Mars is needed for many reasons. It is needed to help unfold the results of the Mars-2001 orbiter's gamma-ray spectrometer (GRS) and neutron spectrometers (NS) to determine elemental abundances on the Martian surface. It is needed to interpret the measurements of the Martian Radiation Environment Experiments (MARIE) on both the Mars 2001 orbiter and lander. It is needed to calculate production rates of cosmogenic nuclides that will be measured in samples returned from Mars. It is needed to determine the doses that astronauts would receive in Martian orbit and especially on the surface of Mars. We discuss the two types of energetic particles in the vicinity of Mars and the nature of their interactions. Solar energetic particles (SEPs) occur very rarely but can have high fluxes that are dangerous in space. However, their energies are low enough that few solar energetic particles reach the surface of Mars. Their interactions can be fairly easily modeled because SEPs create few secondary particles. Galactic cosmic rays (GCRs) have high energies and are the dominant source of energetic particles on the Martian surface, mainly secondary neutrons. Modeling their interactions is complicated because of the range of nuclei in the GCR and their high energies. Work at Los Alamos on GCR interactions will be presented.

Reedy, R. C.↗
DOE OSTI2023

Decay Dose Shielding Analysis with Hybrid Unstructured Mesh/Constructive Solid Geometry Monte Carlo Calculation and ADVANTG Acceleration

Here, the target segments of the Oak Ridge National Laboratory Second Target Station (STS) neutron production facility become highly activated due to spallation reactions or nuclei transmutation by primary protons and emitted neutrons. Once the target segments are removed from their location within the core vessel, decay dose rates must be accurately quantified to determine the shielding configurations of remote-handling tools and transport casks and to aid in planning maintenance activities. For this analysis, we utilized a hybrid unstructured mesh (UM)/constructive solid geometry approach for calculating spallation products and neutron fluxes, activation calculations using the AARE package that includes the CINDER2008 activation code to calculate the decay photon source at different cooling times, and the ADVANTG code to accelerate the final decay photon transport calculation. Both Type 316 stainless steel (SS-316) and lead were investigated as candidates for shielding materials. The decay photon transport calculation through the thick SS-316 or lead shields exhibited between 25 and 30 orders-of-magnitude attenuations in the radial direction, depending on the shield. Such a difficult shielding calculation required advanced variance reduction. ADVANTG has some missing features, which limits its usability in spallation neutron source applications. It does not support volumetric sources created for MCNP6.2 UM capability. An approximate source was created for this problem. Not only was this approximate source needed for running the ADVANTG calculation to generate the weight windows, but also it was essential to develop source biasing (SB) parameters that were crucial for dramatically accelerating the decay photon transport in this problem. With this approximate source, the analysis was completed in a very reasonable computational time, and the design of the STS remote-handling equipment was finalized. This paper compares the efficiency of Monte Carlo simulations with different weight window and SB parameters calculated using different approximate ADVANTG calculations.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
NASA NTRS2007

Evaluating Shielding Effectiveness for Reducing Space Radiation Cancer Risks

We discuss calculations of probability distribution functions (PDF) representing uncertainties in projecting fatal cancer risk from galactic cosmic rays (GCR) and solar particle events (SPE). The PDF s are used in significance tests of the effectiveness of potential radiation shielding approaches. Uncertainties in risk coefficients determined from epidemiology data, dose and dose-rate reduction factors, quality factors, and physics models of radiation environments are considered in models of cancer risk PDF s. Competing mortality risks and functional correlations in radiation quality factor uncertainties are treated in the calculations. We show that the cancer risk uncertainty, defined as the ratio of the 95% confidence level (CL) to the point estimate is about 4-fold for lunar and Mars mission risk projections. For short-stay lunar missions (<180 d), SPE s present the most significant risk, however one that is mitigated effectively by shielding, especially for carbon composites structures with high hydrogen content. In contrast, for long duration lunar (>180 d) or Mars missions, GCR risks may exceed radiation risk limits, with 95% CL s exceeding 10% fatal risk for males and females on a Mars mission. For reducing GCR cancer risks, shielding materials are marginally effective because of the penetrating nature of GCR and secondary radiation produced in tissue by relativistic particles. At the present time, polyethylene or carbon composite shielding can not be shown to significantly reduce risk compared to aluminum shielding based on a significance test that accounts for radiobiology uncertainties in GCR risk projection.

Cucinotta, Francis A.↗
NASA NTRS2017

Simulation of Galactic Cosmic Rays and Dose-Rate Effects in RITRACKS

The NASA Space Radiation Laboratory (NSRL) facility has been used successfully for many years to generate ion beams for radiation research experiments by NASA investigators. Recently, modifications were made to the beam lines to allow rapid switching between different types of ions and energies, with the aim to simulate the Galactic Cosmic Rays (GCR) environment. As this will be a focus of space radiation research for upcoming years, the stochastic radiation track structure code RITRACKS (Relativistic Ion Tracks) was modified to simulate beams of various ion types and energies during time intervals specified by the user at the microscopic and nanoscopic scales. For example, particle distributions of a mixed 344.1-MeV protons (18.04 cGy) and 950-MeV/n iron (5.64 cGy) beam behind a 20 g/cm(exp 2) aluminum followed by a 10 g/cm(exp 2) polyethylene shield as calculated by the code GEANT4 were used as an input field in RITRACKS. Similarly, modifications were also made to simulate a realistic radiation environment in a spacecraft exposed to GCR by sampling the ion types and energies from particle spectra pre-calculated by the code HZETRN. The newly implemented features allows RITRACKS to generate time-dependent differential and cumulative 3D dose voxel maps. These new capabilities of RITRACKS will be used to investigate dose-rate effects and synergistic interactions of various types of radiations for many end points at the microscopic and nanoscopic scales such as DNA damage and chromosome aberrations.

Plante, Ianik↗
NASA NTRS2005

Protective effect of apigenin on radiation-induced chromosomal damage in human lymphocytes

The potential use of flavonoids as a radioprotector is of increasing interest because of their high antioxidant activity and abundance in the diet. The aim of this study is to examine genotoxic and radioprotective effects of one of the most common flavonoids, apigenin, on radiation-induced chromosome aberrations in human lymphocytes. The cytokinesis-block micronucleus (CBMN) assay was used to evaluate such effects of apigenin. Blood samples were collected from two non-smoking healthy male volunteers who had no history of previous exposure to other clastogenic agents. Isolated lymphocytes were cultured. There were two tubes per concentration for all treatments. To evaluate the genotoxicity of apigenin, cells were first treated with different concentrations of apigenin (0, 2.5, 5, 10 and 25 microg/mL) at 24 h after culture initiation, followed by cytochalasin-B (Cyt-B) treatment (3 microg/mL) and cell harvest at 44 and 72 h, respectively. Secondly, to investigate the radioprotective effect, cell cultures were exposed to different concentrations of apigenin as described above for 30 min before being irradiated to 2 Gy of 137Cs gamma rays (at a dose rate of 0.75 Gy/min). In all instances, the frequency of MN was scored in binucleated (BN) cells. The nuclear proliferation index also was calculated. We did not detect an increase in the frequency of MN in non-irradiated human lymphocyte cultures treated with 2.5, 5.0 or 10 microg/mL apigenin; although, we did observe an increase in cultures treated with 25 microg/mL apigenin (the highest concentration of apigenin used in our study). We also observed a significant increase in the frequency of MN in irradiated cells overall; however, the frequency was decreased as the concentration of apigenin increased, suggesting a radioprotective effect. These findings provide a basis for additional studies to help clarify the potential use and benefit of apigenin as a radioprotector.

NASA Discipline Radiation Health↗
NASA NTRS1991

Radiation risk predictions for Space Station Freedom orbits

Risk assessment calculations are presented for the preliminary proposed solar minimum and solar maximum orbits for Space Station Freedom (SSF). Integral linear energy transfer (LET) fluence spectra are calculated for the trapped proton and GCR environments. Organ dose calculations are discussed using the computerized anatomical man model. The cellular track model of Katz is applied to calculate cell survival, transformation, and mutation rates for various aluminum shields. Comparisons between relative biological effectiveness (RBE) and quality factor (QF) values for SSF orbits are made.

Cucinotta, Francis A.↗
NASA NTRS1995

Image analysis used to count and measure etched tracks from ionizing radiation

We have developed techniques to use digitized scanning electron micrographs and computer image analysis programs to measure track densities in lunar soil grains and plastic dosimeters. Tracks in lunar samples are formed by highly ionizing solar energetic particles and cosmic rays during near surface exposure on the Moon. The track densities are related to the exposure conditions (depth and time). Distributions of the number of grains as a function of their track densities can reveal the modality of soil maturation. We worked on two samples identified for a consortium study of lunar weathering effects, 61221 and 67701. They were prepared by the lunar curator's staff as polished grain mounts that were etched in boiling 1 N NaOH for 6 h to reveal tracks. We determined that backscattered electron images taken at 10 percent contrast and approximately 50 percent brightness produced suitable high contrast images for analysis. We used the NIH Image program to cut out areas that were unsuitable for measurement such as edges, cracks, etc. We ascertained a gray-scale threshold of 25 to separate tracks from background. We used the computer to count everything that was two pixels or greater in size and to measure the area to obtain track densities. We found an excellent correlation with manual measurements for track densities below 1 x 10(exp 8) cm(exp -2). For track densities between 1 x 10(exp 8) cm(exp -2) to 1 x 10(exp 9) cm(exp -2) we found that a regression formula using the percentage area covered by tracks gave good agreement with manual measurements. We determined the track density distributions for 61221 and 67701. Sample 61221 is an immature sample, but not pristine. Sample 67701 is a submature sample that is very close to being fully mature. Because only 10 percent of the grains have track densities less than 10(exp 9) cm(exp -2), it is difficulty to determine whether the sample matured in situ or is a mixture of a mature and a submature soil. Although our analysis of plastic dosimeters is at an early stage of development, results are encouraging. The dosimeter was etched in 6.25 N NaOH at 70 deg C for 16 h. We took 200x secondary electron images of the sample and used the NIH Image software to count and measure major and minor diameters of the etched tracks. We calculated the relative track etch rate from a formula that relates it to the major and minor diameters. We made a histogram of the number of tracks versus their relative etch rate. The relative track etching rate is proportional to the linear energy transfer of the particle. With appropriate calibration experiments, the histogram could be used to calculate the radiation dose.

Blanford, George E.↗
NASA NTRS2004

A space radiation shielding model of the Martian radiation environment experiment (MARIE)

The 2001 Mars Odyssey spacecraft was launched towards Mars on April 7, 2001. Onboard the spacecraft is the Martian radiation environment experiment (MARIE), which is designed to measure the background radiation environment due to galactic cosmic rays (GCR) and solar protons in the 20-500 MeV/n energy range. We present an approach for developing a space radiation-shielding model of the spacecraft that includes the MARIE instrument in the current mapping phase orientation. A discussion is presented describing the development and methodology used to construct the shielding model. For a given GCR model environment, using the current MARIE shielding model and the high-energy particle transport codes, dose rate values are compared with MARIE measurements during the early mapping phase in Mars orbit. The results show good agreement between the model calculations and the MARIE measurements as presented for the March 2002 dataset. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Center JSC↗
DOE OSTI2020

Extension of OpenMC for Fixed Source Transmutation Calculations

This report documents work performed under a Strategic Partnership Project between Argonne National Laboratory (ANL) and the United Kingdom Atomic Energy Authority (UKAEA). The overall goal of this project is to extend OpenMC [1], a community-developed Monte Carlo particle transport code, to be able to perform fixed-source transmutation calculations. In fission and fusion reactors, the high flux of energetic neutrons causes materials within the reactor to “transmute,” or undergo a nuclear reaction that results in the addition/removal of neutrons and protons from the nucleus of an atom. If subjected to these reactions for long enough, the overall composition and physical properties of the material itself begin to change as a result of transmutation. Such a feature is vital for predicting the decrease in tritium production rate within a breeder blanket during the lifetime of a fusion reactor. OpenMC is capable of simulating neutron transport in fission/fusion systems, thereby allowing it to estimate the flux that causes transmutation. It is also capable of solving the transmutation equations, which determine how the composition of a material changes over time due to neutron irradiation and radioactive decay. However, solving the transmutation equations was previously only possible when the source of neutrons came from a fission system. In a fusion system, the source of neutrons is typically determined by a separate code and then given as an input to the particle transport simulation. This is known as a fixed source calculation. Through this project, we have extended OpenMC to solve the transmutation equations for a fixed source calculation. Evaluating the change in material compositions due to transmutation and its effect on physical properties is of key importance to a range of engineering analyses for fission and fusion systems. For example, in a fusion reactor, estimating the dose rate at different physical locations resulting from irradiated materials in the reactor allows designers to ensure that workers are not exposed to doses beyond applicable regulations. In order to properly dispose of irradiated materials, designers also need to estimate the radiotoxicity, which again relies on knowledge of the material composition at some future time. The specific tasks for this project that were agreed to between ANL and UKAEA were as follows: 1. Make changes and additions in the openmc.deplete and related modules in OpenMC to support transmutation calculations following a fixed source transport simulation. 2. Make necessary changes to OpenMC to model transmutation due to an arbitrary set of reactions needed for fusion applications. Use this new capability to generate a depletion chain file based on the TENDL nuclear data library. 3. Improve the openmc.deplete module in OpenMC to keep track of gases produced as a by-product of nuclear reactions during transmutation calculations. 4. Validate the new capabilities by carrying out fixed-source transmutation calculations on a suitable benchmark problem using OpenMC and a comparable Monte Carlo neutron transport code.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2022

Verification and Validation Tests of the Gamma Library of the ARC Software Package (Rev.1)

As part of the verification and validation (V&V) efforts of the Argonne Reactor Code (ARC) software system to support the Versatile Test Reactor (VTR) project of the U.S. Department of Energy (DOE), work has been performed to verify and validate the gamma (or photon) library of the multigroup cross section generation code MC 2 -3 of the ARC system, which is the essential part of the coupled neutron and gamma heating calculations to determine the heat generation rate or power distribution in the core. This V&V study was carried out in three steps: 1) review of the procedures and utility programs for generating the MC 2 -3 gamma library, 2) verification tests of cross sections and KERMA factors by comparing the total heat generation rate of coupled neutron and gamma calculation with that obtained with reaction Q values under the assumption of local gamma energy deposition and by comparing the prompt heat generation rate with that calculated with the MCNP6.2 code, and 3) validation tests of cross sections and KERMA factors by analyzing the ZPPR-15D gamma dose data measured with thermoluminescent dosimeters (TLD).

22 GENERAL STUDIES OF NUCLEAR REACTORS↗
NASA NTRS1973

Solar flare proton spectrum averaged over the last 5000 years

The solar flare differential energy spectrum and integral proton flux above 10 MeV averaged over the last several thousand years are derived from thermoluminescence (TL) data. The dose-rate depth profile is obtained using a new TL equilibrium technique which is independent of the TL decay kinetics. The dose-rate depth profile produced by solar flare protons with a differential energy spectrum of the form dJ/dE = KE to the minus gamma power is calculated for arbitrary gamma. The best fit to the TL data in rock 14310 is obtained for gamma = 2.3 plus or minus 0.2 and an omnidirectional (4 pi) integral flux above 10 MeV of 40 to 80 prot/sq cm/sec. The TL half-life is determined to be 2000 yr. These results are compared to those for Na-22 (half-life of. 2.6 yr) and Al-26 (half-life of 740,000 yr) obtained by Wahlen et al. (1972) and Rancitelli et al. (1972), and it is concluded that the spectral shape and flux of protons in the interval from 25 to 100 MeV is the same within experimental errors when averaged over these three very different time periods.

Hoyt, H. P., Jr.↗
NASA NTRS1998

Environmental Radiation Measurements on the Mir Space Station: Internal Experiment Program - Program 1

As part of the NASA/Mir Phase 1B Science Program, the ionizing radiation environment inside and outside the Russian Mir's Space Station was monitored using a combination of Thermoluminescent Detectors (TLD) and CR-39 Plastic Nuclear Track Detectors (PNTD). Radiation measurements inside the Mir station were carried out using six Area Passive Dosimeters (APD), four located inside the Mir Base Block and two located inside the Kvant 2 module, during the NASA-2/Mir-21, NASA-3/Mir-22 and NASA-4/Mir-23 missions. The radiation environment under low shielding was measured using an External Dosimeter Array (EDA) mounted on the outer surface of the Kvant 2 module. The external radiation environment and a location inside the Kvant 2 roughly corresponding to the location of the EDA were monitored for 130 days during the NASA- 4/Mir-23 and NASA-5/Mir-24 missions. Dose rates measured by APD TLDs ranged from 271 to 407 microGy/d during the NASA-2/Mir-21 mission, from 265 to 378 microGy/d during the NASA-3/Mir-22 mission, and from 287 to 421 microGy/d during the NASA-4/Mir-23 mission. APD PNTDs have been analyzed and LET spectra have been Cenerated for the five APDs exposed on the NASA-2/Mir-21 mission and for two APD PNTDs exposed on the NASA-3/Mir-22 mission. Dose equivalent rates on the NASA-2/Mir-21 mission ranged from 513 microSv/d in the Kvant 2 module to 710 microSv/d on the floor of the Base Block. Dose as a function of shielding depth in TLDs has been measured in the thin TLD stacks including in the EDA. EDA dose range from 72.5 Gy under 0.0146 g/sq cm to 0.093 Gy under 3.25 g/sq cm of shielding. Readout and analysis of the reaming PNTDs form the NASA-3/Mir-22 mission and PNTDs from the NASA-4/Mir-23 mission (including those from the EDA) is ongoing and will be completed during the final year of this experiment. Dose equivalent rates for the NASA-3/Mir-22 and NASA-4/Mir-23 APDs will then be determined and comparisons will be made with both model calculations and with results from similar measurements.

Benton, E. V.↗
DOE OSTI2022

Decay Dose Shielding Analysis with Hybrid Unstructured Mesh/Constructive Solid Geometry Monte Carlo Calculation and ADVANTG Acceleration

The Oak Ridge National Laboratory (ORNL) Second Target Station (STS) neutron production facility is an accelerator driven pulsed neutron source that is currently being actively developed at ORNL. The neutrons are produced by proton-induced spallation reactions. A proton beam of 700 kW power is delivered to a spallation target in short, less than 1 µs long pulses, with 15 Hz repetition rate. The spallation target of ORNL STS is a rotating water-cooled tungsten target with tantalum cladding housed in a stainless-steel shroud. It is divided into 21 segments. These segments become highly activated due to spallation reactions or nuclei transmutation by the emitted neutrons. The radioactive nuclides continue to decay after ceasing operation. The decay dose rates generated from the target segments once they are removed from their operational location within the core vessel must be accurately quantified to determine the shielding configurations of remote handling tools and transport casks and to aid in planning maintenance events. To determine the shielding configurations needed for an activated target segment after ceasing operation, both the hybrid unstructured mesh (UM)/constructive solid geometry (CSG) approach that was previously utilized for STS analyses [1] and the ADVANTG code [2] were used. Even though the ADVANTG code does not include UM capability, the utilization of its advanced variance reduction technique was crucial to accelerate the extremely difficult final photon transport calculation in this analysis. This paper also describes the procedures taken to mitigate the convergence issues that occur when ADVANTG uses a source definition that does not match the source of the final Monte Carlo (MC) calculation. These convergence issues often occur because of inconsistencies between source and transport biasing parameters.

Ibrahim, Ahmad↗
DOE OSTI2026

Tank 11H Low Temperature Aluminum Dissolution and Inhalation Dose Potential Analyses at Savannah River Site – 26018

Currently, there is approximately 34 million gallons of high-level radioactive tank waste in the Tank Farm at the Savannah River Site (SRS). The ultimate goal of operations at the Tank Farm is to remove the high level waste (HLW) from the tanks followed by stabilization of the waste through vitrification of the HLW into glass or grouting the decontaminated waste into saltstone. After bulk removal of the HLW consisting of sludge, saltcake, and supernatant, further efforts are made to reduce the residual waste present in the tank in order to declare preliminary cease waste removal (PCWR) signifying completion of HLW removal. These reduction efforts can include tank washing to remove soluble salts and radioisotopes and dissolution of solids including aluminum. Aluminum in the form of gibbsite and boehmite is relatively insoluble in water. Through addition of aqueous sodium hydroxide, the aluminum can be dissolved at mild temperatures. In order for the waste tank to meet closure mode requirements of the Concentration, Storage, and Transfer Facilities (CSTF), which includes the Tank Farm, Documented Safety Analysis (DSA), a component of the safety basis, the inhalation dose potential (IDP) and the radiolytic hydrogen generation rate of the stored waste must be demonstrated to be lower than their respective designated limits. These parameters are calculated from measured radiochemical analyses of isotopes that emit a high amount of radioactivity including Cs-137, Sr-90, Pu-238, Pu-239, Pu-240, Pu-241, Am-241, and Cm-244. Following the low temperature aluminum dissolution (LTAD) process, Tank 11H slurry samples were pulled from the tank and sent to Savannah River National Laboratory (SRNL) to measure the extent of aluminum dissolution, hydroxide concentration, densities of slurry and supernatant, weight percent solids analyses, and radionuclide activities. The analyses of the composite sample found that approximately 90% of the total aluminum in the slurry was dissolved, indicating successful reduction of the insoluble aluminum in the waste tank. Additionally, the weight percent insoluble solids (slurry basis) measurement of the composite sample was found to be approximately 1%, demonstrating that minimal solids still remain in the tank. Finally, the radiochemical analyses of the composite sample determined that the waste contents of the tank met the IDP and radiolytic hydrogen generation rate requirements of the CSTF DSA. These measurements have shown that the LTAD process in Tank 11H was successful in waste reduction efforts and a positive step towards declaring PCWR and tank closure at SRS.

Dekarske, John [Savannah River National Laboratory↗
DOE OSTI2020

High-throughput screening tools facilitate calculation of a combined exposure-bioactivity index for chemicals with endocrine activity

High-throughput and computational tools provide a new opportunity to calculate combined bioactivity of exposure to diverse chemicals acting through a common mechanism. We used high throughput in vitro bioactivity data and exposure predictions from the U.S. EPA’s Toxicity and Exposure Forecaster (ToxCast and ExpoCast) to estimate combined estrogen receptor (ER) agonist activity of non-pharmaceutical chemical exposures for the general U.S. population. High-throughput toxicokinetic (HTTK) data provide conversion factors that relate bioactive concentrations measured in vitro (µM), to predicted population geometric mean exposure rates (mg/kg/day). These data were available for 22 chemicals with ER agonist activity and were estimated for other ER bioactive chemicals based on the geometric mean of HTTK values across chemicals. For each chemical, ER bioactivity across ToxCast assays was compared to predicted population geometric mean exposure at different levels of in vitro potency and model certainty. Dose additivity was assumed in calculating a Combined Exposure-Bioactivity Index (CEBI), the sum of exposure/bioactivity ratios. Combined estrogen bioactivity was also calculated in terms of the percent maximum bioactivity of chemical mixtures in human plasma using a concentration-addition model. Estimated CEBIs vary greatly depending on assumptions used for exposure and bioactivity. In general, CEBI values were <1 when using median of the estimated general population chemical intake rates, while CEBI were ≥1 when using the upper 95th confidence bound for those same intake rates for all chemicals. Concentration-addition model predictions of mixture bioactivity yield comparable results. Based on current in vitro bioactivity data, HTTK methods, and exposure models, combined exposure scenarios sufficient to influence estrogen bioactivity in the general population cannot be ruled out. Future improvements in screening methods and computational models could reduce uncertainty and better inform the potential combined effects of estrogenic chemicals.

54 ENVIRONMENTAL SCIENCES↗