•This publication is designed to update the RIFM safety assessment process, which follows a series of decision trees.•This process incorporates advances in approaches in risk assessment used by RIFM ...over the past ten years.•A framework for choosing structural analogs and consideration of the Threshold of Toxicological Concern (TTC) are included.•Quantitative Risk Assessment (QRA) for dermal sensitization and aggregate exposure assessment methodologies are included.•The latest alternatives to animal testing methodology and environmental risk assessment are included.
The Research Institute for Fragrance Materials, Inc. (RIFM) has been engaged in the generation and evaluation of safety data for fragrance materials since its inception over 45 years ago. Over time, RIFM's approach to gathering data, estimating exposure and assessing safety has evolved as the tools for risk assessment evolved. This publication is designed to update the RIFM safety assessment process, which follows a series of decision trees, reflecting advances in approaches in risk assessment and new and classical toxicological methodologies employed by RIFM over the past ten years. These changes include incorporating 1) new scientific information including a framework for choosing structural analogs, 2) consideration of the Threshold of Toxicological Concern (TTC), 3) the Quantitative Risk Assessment (QRA) for dermal sensitization, 4) the respiratory route of exposure, 5) aggregate exposure assessment methodology, 6) the latest methodology and approaches to risk assessments, 7) the latest alternatives to animal testing methodology and 8) environmental risk assessment. The assessment begins with a thorough analysis of existing data followed by in silico analysis, identification of ‘read across’ analogs, generation of additional data through in vitro testing as well as consideration of the TTC approach. If necessary, risk management may be considered.
All ten LIGO/Virgo binary black hole (BH-BH) coalescences reported following the O1/O2 runs have near-zero effective spins. There are only three potential explanations for this. If the BH spin ...magnitudes are large, then: (i) either both BH spin vectors must be nearly in the orbital plane or (ii) the spin angular momenta of the BHs must be oppositely directed and similar in magnitude. Then there is also the possibility that (iii) the BH spin magnitudes are small. We consider the third hypothesis within the framework of the classical isolated binary evolution scenario of the BH-BH merger formation. We test three models of angular momentum transport in massive stars: a mildly efficient transport by meridional currents (as employed in the Geneva code), an efficient transport by the Tayler-Spruit magnetic dynamo (as implemented in the MESA code), and a very-efficient transport (as proposed by Fuller et al.) to calculate natal BH spins. We allow for binary evolution to increase the BH spins through accretion and account for the potential spin-up of stars through tidal interactions. Additionally, we update the calculations of the stellar-origin BH masses, including revisions to the history of star formation and to the chemical evolution across cosmic time. We find that we can simultaneously match the observed BH-BH merger rate density and BH masses and BH-BH effective spins. Models with efficient angular momentum transport are favored. The updated stellar-mass weighted gas-phase metallicity evolution now used in our models appears to be key for obtaining an improved reproduction of the LIGO/Virgo merger rate estimate. Mass losses during the pair-instability pulsation supernova phase are likely to be overestimated if the merger GW170729 hosts a BH more massive than 50
M
⊙
. We also estimate rates of black hole-neutron star (BH-NS) mergers from recent LIGO/Virgo observations. If, in fact. angular momentum transport in massive stars is efficient, then any (electromagnetic or gravitational wave) observation of a rapidly spinning BH would indicate either a very effective tidal spin up of the progenitor star (homogeneous evolution, high-mass X-ray binary formation through case A mass transfer, or a spin- up of a Wolf-Rayet star in a close binary by a close companion), significant mass accretion by the hole, or a BH formation through the merger of two or more BHs (in a dense stellar cluster).
We present a near-infrared spectral sequence of the electromagnetic counterpart to the binary neutron star merger GW170817 detected by Advanced Laser Interferometer Gravitational-wave Observatory ...(LIGO)/Virgo. Our data set comprises seven epochs of J+H spectra taken with FLAMINGOS-2 on Gemini-South between 1.5 and 10.5 days after the merger. In the initial epoch, the spectrum is dominated by a smooth blue continuum due to a high-velocity, lanthanide-poor blue kilonova component. Starting the following night, all of the subsequent spectra instead show features that are similar to those predicted in model spectra of material with a high concentration of lanthanides, including spectral peaks near 1.07 and 1.55 m. Our fiducial model with 0.04 M of ejecta, an ejection velocity of v = 0.1c, and a lanthanide concentration of Xlan = 10−2 provides a good match to the spectra taken in the first five days, although it over-predicts the late-time fluxes. We also explore models with multiple fitting components, in each case finding that a significant abundance of lanthanide elements is necessary to match the broad spectral peaks that we observe starting at 2.5 days after the merger. These data provide direct evidence that binary neutron star mergers are significant production sites of even the heaviest r-process elements.
We report the discovery and monitoring of the near-infrared counterpart (AT2017gfo) of a binary neutron-star merger event detected as a gravitational wave source by Advanced Laser Interferometer ...Gravitational-wave Observatory (LIGO)/Virgo (GW170817) and as a short gamma-ray burst by Fermi Gamma-ray Burst Monitor (GBM) and Integral SPI-ACS (GRB 170817A). The evolution of the transient light is consistent with predictions for the behavior of a "kilonova/macronova" powered by the radioactive decay of massive neutron-rich nuclides created via r-process nucleosynthesis in the neutron-star ejecta. In particular, evidence for this scenario is found from broad features seen in Hubble Space Telescope infrared spectroscopy, similar to those predicted for lanthanide-dominated ejecta, and the much slower evolution in the near-infrared K s -band compared to the optical. This indicates that the late-time light is dominated by high-opacity lanthanide-rich ejecta, suggesting nucleosynthesis to the third r-process peak (atomic masses A 195 ). This discovery confirms that neutron-star mergers produce kilo-/macronovae and that they are at least a major-if not the dominant-site of rapid neutron capture nucleosynthesis in the universe.
BACKGROUND AND PURPOSE Asthma is characterized by reversible bronchoconstriction and airway hyperreactivity. Although M3 muscarinic receptors mediate bronchoconstriction, non‐selective muscarinic ...receptor antagonists are not currently recommended for chronic control of asthma. We tested whether selective blockade of M3 receptors, at the time of antigen challenge, blocks subsequent development of airway hyperreactivity in antigen‐challenged guinea‐pigs.
EXPERIMENTAL APPROACH Ovalbumin‐sensitized guinea‐pigs were pretreated with 1 µg·kg−1 of a kinetically selective M3 receptor antagonist, tiotropium, or 1 mg·kg−1 of a non‐selective muscarinic receptor antagonist, atropine, and challenged with inhaled ovalbumin. Animals were anaesthetized, paralyzed, ventilated and vagotomized 24 h later. We measured vagally mediated bronchoconstriction and i.v. ACh‐induced bronchoconstriction.
KEY RESULTS Electrical stimulation of both vagus nerves induced frequency‐dependent bronchoconstriction in sensitized animals that was significantly increased after antigen challenge. Antigen‐induced hyperreactivity was completely blocked by tiotropium pretreatment but only partially blocked by atropine pretreatment. Surprisingly, although tiotropium blocked bronchoconstriction induced by i.v. ACh, it did not inhibit vagally‐induced bronchoconstriction in sensitized controls, suggesting that tiotropium does not block hyperreactivity by blocking receptors for vagally released ACh. Rather, tiotropium may have worked through an anti‐inflammatory mechanism, since it inhibited eosinophil accumulation in the lungs and around nerves.
CONCLUSIONS AND IMPLICATIONS These data confirm that testing M3 receptor blockade with exogenous ACh does not predict vagal blockade. Our data also suggest that selective blockade of M3 receptors may be effective in asthma via mechanisms that are separate from inhibition of bronchoconstriction.
•Acetyl cedrene; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, read-across, ...and/or TTC.
We present the Dark Energy Camera (DECam) discovery of the optical counterpart of the first binary neutron star merger detected through gravitational-wave emission, GW170817. Our observations ...commenced 10.5 hr post-merger, as soon as the localization region became accessible from Chile. We imaged 70 deg2 in the i and z bands, covering 93% of the initial integrated localization probability, to a depth necessary to identify likely optical counterparts (e.g., a kilonova). At 11.4 hr post-merger we detected a bright optical transient located from the nucleus of NGC 4993 at redshift z = 0.0098, consistent (for km s−1 Mpc−1) with the distance of 40 8 Mpc reported by the LIGO Scientific Collaboration and the Virgo Collaboration (LVC). At detection the transient had magnitudes of and , and thus an absolute magnitude of , in the luminosity range expected for a kilonova. We identified 1500 potential transient candidates. Applying simple selection criteria aimed at rejecting background events such as supernovae, we find the transient associated with NGC 4993 as the only remaining plausible counterpart, and reject chance coincidence at the 99.5% confidence level. We therefore conclude that the optical counterpart we have identified near NGC 4993 is associated with GW170817. This discovery ushers in the era of multi-messenger astronomy with gravitational waves and demonstrates the power of DECam to identify the optical counterparts of gravitational-wave sources.
We present UV, optical, and near-infrared (NIR) photometry of the first electromagnetic counterpart to a gravitational wave source from Advanced Laser Interferometer Gravitational-wave Observatory ...(LIGO)/Virgo, the binary neutron star merger GW170817. Our data set extends from the discovery of the optical counterpart at 0.47-18.5 days post-merger, and includes observations with the Dark Energy Camera (DECam), Gemini-South/FLAMINGOS-2 (GS/F2), and the Hubble Space Telescope (HST). The spectral energy distribution (SED) inferred from this photometry at 0.6 days is well described by a blackbody model with T 8300 K, a radius of R 4.5 × 10 14 cm (corresponding to an expansion velocity of v 0.3 c ), and a bolometric luminosity of L bol 5 × 10 41 erg s−1. At 1.5 days we find a multi-component SED across the optical and NIR, and subsequently we observe rapid fading in the UV and blue optical bands and significant reddening of the optical/NIR colors. Modeling the entire data set, we find that models with heating from radioactive decay of 56Ni, or those with only a single component of opacity from r-process elements, fail to capture the rapid optical decline and red optical/NIR colors. Instead, models with two components consistent with lanthanide-poor and lanthanide-rich ejecta provide a good fit to the data; the resulting "blue" component has M ej blue 0.01 M and v ej blue 0.3 c , and the "red" component has M ej red 0.04 M and v ej red 0.1 c . These ejecta masses are broadly consistent with the estimated r-process production rate required to explain the Milky Way r-process abundances, providing the first evidence that binary neutron star (BNS) mergers can be a dominant site of r-process enrichment.
•Menthyl acetate (isomer unspecified); a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target ...data, read-across, and/or TTC.
•Mandarin oil terpenes; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, ...read-across, and/or TTC.
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