Search

Non-targeted analysis (NTA) methods are widely used for chemical discovery but seldom employed for quantitation due to a lack of robust methods to estimate chemical concentrations with confidence limits. Herein, we present and evaluate new statistical methods for quantitative NTA (qNTA) using high-resolution mass spectrometry (HRMS) data from EPA's Non-Targeted Analysis Collaborative Trial (ENTACT). Experimental intensities of ENTACT analytes were observed at multiple concentrations using a semi-automated NTA workflow. Chemical concentrations and corresponding confidence limits were first estimated using traditional calibration curves. Two qNTA estimation methods were then implemented using experimental response factor (RF) data (where RF = intensity/concentration). The bounded response factor method used a non-parametric bootstrap procedure to estimate select quantiles of training set RF distributions. Quantile estimates then were applied to test set HRMS intensities to inversely estimate concentrations with confidence limits. The ionization efficiency estimation method restricted the distribution of likely RFs for each analyte using ionization efficiency predictions. Given the intended future use for chemical risk characterization, predicted upper confidence limits (protective values) were compared to known chemical concentrations. Using traditional calibration curves, 95% of upper confidence limits were within ~tenfold of the true concentrations. The error increased to ~60-fold (ESI+) and ~120-fold (ESI-) for the ionization efficiency estimation method and to ~150-fold (ESI+) and ~130-fold (ESI-) for the bounded response factor method. This work demonstrates successful implementation of confidence limit estimation strategies to support qNTA studies and marks a crucial step towards translating NTA data in a risk-based context., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

High-resolution mass spectrometry (HRMS) enables rapid chemical annotation via accurate mass measurements and matching of experimentally derived spectra with reference spectra. Reference libraries are generated from chemical standards and are therefore limited in size relative to known chemical space. To address this limitation, in silico spectra (i.e., MS/MS or MS2 spectra), predicted via Competitive Fragmentation Modeling-ID (CFM-ID) algorithms, were generated for compounds within the U.S. Environmental Protection Agency's (EPA) Distributed Structure-Searchable Toxicity (DSSTox) database (totaling, at the time of analysis, ~ 765,000 substances). Experimental spectra from EPA's Non-Targeted Analysis Collaborative Trial (ENTACT) mixtures (n = 10) were then used to evaluate the performance of the in silico spectra. Overall, MS2 spectra were acquired for 377 unique compounds from the ENTACT mixtures. Approximately 53% of these compounds were correctly identified using a commercial reference library, whereas up to 50% were correctly identified as the top hit using the in silico library. Together, the reference and in silico libraries were able to correctly identify 73% of the 377 ENTACT substances. When using the in silico spectra for candidate filtering, an examination of binary classifiers showed a true positive rate (TPR) of 0.90 associated with false positive rates (FPRs) of 0.10 to 0.85, depending on the sample and method of candidate filtering. Taken together, these findings show the abilities of in silico spectra to correctly identify true positives in complex samples (at rates comparable to those observed with reference spectra), and efficiently filter large numbers of potential false positives from further consideration. Graphical abstract.

Non-targeted analysis (NTA) methods are increasingly used to discover contaminants of emerging concern (CECs), but the extent to which these methods can support exposure and health studies remains to be determined. EPA's Non-Targeted Analysis Collaborative Trial (ENTACT) was launched in 2016 to address this need. As part of ENTACT, 1269 unique substances from EPA's ToxCast library were combined to make ten synthetic mixtures, with each mixture containing between 95 and 365 substances. As a participant in the trial, we first performed blinded NTA on each mixture using liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS). We then performed an unblinded evaluation to identify limitations of our NTA method. Overall, at least 60% of spiked substances could be observed using selected methods. Discounting spiked isomers, true positive rates from the blinded and unblinded analyses reached a maximum of 46% and 65%, respectively. An overall reproducibility rate of 75% was observed for substances spiked into more than one mixture and observed at least once. Considerable discordance in substance identification was observed when comparing a subset of our results derived from two separate reversed-phase chromatography methods. We conclude that a single NTA method, even when optimized, can likely characterize only a subset of ToxCast substances (and, by extension, other CECs). Rigorous quality control and self-evaluation practices should be required of labs generating NTA data to support exposure and health studies. Accurate and transparent communication of performance results will best enable meaningful interpretations and defensible use of NTA data. Graphical abstract ᅟ.

We measured photolysis kinetics of the PAH anthracene in aqueous solution, in bulk ice, and at ice surfaces in the presence and absence of chromophoric dissolved organic matter (CDOM). Self-association, which occurs readily at ice surfaces, may be responsible for the faster anthracene photolysis observed there. Photolysis rate constants in liquid water increased under conditions where anthracene self-association was observed. Concomitantly, kinetics changed from first-order to second-order, indicating that the photolysis mechanism at ice surfaces might be different than that in aqueous solution. Other factors that could lead to faster photolysis at ice surfaces were also investigated. Increased photon fluxes due to scattering in the ice samples can account for at most 20% of the observed rate increase, and other factors including singlet oxygen ( 1 O 2 *) production and changes in pH and polarity were determined not to be responsible for the faster photolysis. CDOM (in the form of fulvic acid (FA)) did not affect anthracene photolysis kinetics in aqueous solution but suppressed photolysis in ice cubes and ice granules (by 30% and 56%, respectively). This was primarily due to competitive photon absorption (the inner filter effect). Freeze-concentration (or "salting out") appears to slightly increase the suppressing effects of FA on anthracene photolysis. This may be due to increased competitive photon absorption or to physical interactions between anthracene and FA.

Chondrules, which are roughly millimeter-sized silicate-rich spherules, dominate the most primitive meteorites, the chondrites. They formed as molten droplets and, judging from their abundances in chondrites, are the products of one of the most energetic processes that operated in the early inner solar system. The conditions and mechanism of chondrule formation remain poorly understood. Here we show that the abundance of the volatile element sodium remained relatively constant during chondrule formation. Prevention of the evaporation of sodium requires that chondrules formed in regions with much higher solid densities than predicted by known nebular concentration mechanisms. These regions would probably have been self-gravitating. Our model explains many other chemical characteristics of chondrules and also implies that chondrule and planetesimal formation were linked.

The bulk of the comet 81P/Wild 2 (hereafter Wild 2) samples returned to Earth by the Stardust spacecraft appear to be weakly constructed mixtures of nanometer-scale grains, with occasional much larger (over 1 micrometer) ferromagnesian silicates, Fe-Ni sulfides, Fe-Ni metal, and accessory phases. The very wide range of olivine and low-Ca pyroxene compositions in comet Wild 2 requires a wide range of formation conditions, probably reflecting very different formation locations in the protoplanetary disk. The restricted compositional ranges of Fe-Ni sulfides, the wide range for silicates, and the absence of hydrous phases indicate that comet Wild 2 experienced little or no aqueous alteration. Less abundant Wild 2 materials include a refractory particle, whose presence appears to require radial transport in the early protoplanetary disk.

The Stardust spacecraft collected thousands of particles from comet 81P/Wild 2 and returned them to Earth for laboratory study. The preliminary examination of these samples shows that the nonvolatile portion of the comet is an unequilibrated assortment of materials that have both presolar and solar system origin. The comet contains an abundance of silicate grains that are much larger than predictions of interstellar grain models, and many of these are high-temperature minerals that appear to have formed in the inner regions of the solar nebula. Their presence in a comet proves that the formation of the solar system included mixing on the grandest scales.

Primitive meteorites provide a glimpse into the early history of our solar system, but some of the most primitive meteorites are also rarely found on Earth. In his Perspective, Grossman explains why the fall of the Tagish Lake meteorite on 18 January 2000 in British Columbia, Canada, was a lucky event for meteorite researchers. The first analysis of the meteorite is reported by Brown et al. Well-preserved organic matter in the meteorite provides a unique opportunity to study the nature and origin of organic matter that may have accreted on early Earth and played a role in the origin of life.

Rhenium and osmium concentrations and the osmium isotopic compositions of iron meteorites were determined by negative thermal ionization mass spectrometry. Data for the IIA iron meteorites define an isochron with an uncertainty of approximately +/-31 million years for meteorites approximately 4500 million years old. Although an absolute rheniumosmium closure age for this iron group cannot be as precisely constrained because of uncertainty in the decay constant of (187)Re, an age of 4460 million years ago is the minimum permitted by combined uncertainties. These age constraints imply that the parent body of the IIAB magmatic irons melted and subsequently cooled within 100 million years after the formation of the oldest portions of chondrites. Other iron meteorites plot above the IIA isocbron, indicating that the planetary bodies represented by these iron groups may have cooled significantly later than the parent body of the IIA irons.