Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Chronic Toxicity of Iron to Aquatic Organisms under Variable pH, Hardness, and Dissolved Organic Carbon Conditions.

A series of chronic toxicity tests was conducted exposing three aquatic species to iron (Fe) in laboratory freshwaters. The test organisms included the green algae Raphidocelis subcapitata, the cladoceran Ceriodaphnia dubia, and the fathead minnow Pimephales promelas. They were exposed to Fe (as Fe (III) sulfate) in waters under varying pH (5.9-8.5), hardness (10.3-255 mg/L CaCO3 ), and dissolved organic carbon (DOC; 0.3-10.9 mg/L) conditions. Measured total Fe was used for calculations of biological effect concentrations because dissolved Fe was only a fraction of nominal and did not consistently increase as total Fe increased. This was indicative of the high concentrations of Fe required to elicit a biological response and that Fe species that did not pass through a 0.20- or 0.45-µm filter (dissolved fraction) contributed to Fe toxicity. The concentrations frequently exceeded the solubility limits of Fe(III) under circumneutral pH conditions relevant to most natural surface waters. Chronic toxicity endpoints (10% effect concentrations [EC10s]) ranged from 442 to 9607 µg total Fe/L for R. subcapitata growth, from 383 to 15 947 µg total Fe/L for C. dubia reproduction, and from 192 to 58,308 µg total Fe/L for P. promelas growth. Toxicity to R. subcapitata was variably influenced by all three water quality parameters, but especially DOC. Toxicity to C. dubia was influenced by DOC, less so by hardness, but not by pH. Toxicity to P. promelas was variable, but greatest under low hardness, low pH, and low DOC conditions. These data were used to develop an Fe-specific, bioavailability-based multiple linear regression model as part of a companion publication. Environ Toxicol Chem 2023;42:1371-1385. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Absolute and Relative Vaccine Effectiveness of Primary and Booster Series of COVID-19 Vaccines (mRNA and Adenovirus Vector) Against COVID-19 Hospitalizations in the United States, December 2021-April 2022.

Background: Coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines. Methods: Booster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE. Results: A total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary. Conclusions: Vaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.

Effectiveness of the Ad26.COV2.S (Johnson & Johnson) Coronavirus Disease 2019 (COVID-19) Vaccine for Preventing COVID-19 Hospitalizations and Progression to High Disease Severity in the United States.

Background . Adults in the United States (US) began receiving the adenovirus vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use. Methods . In a multicenter case-control analysis of US adults (≥18 years) hospitalized 11 March to 15 December 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression. Results . After excluding patients receiving mRNA vaccines, among 3979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% confidence interval [CI]: 63-75%) overall, including 55% (29-72%) among immunocompromised patients, and 72% (64-77%) among immunocompetent patients, for whom VEs was similar at 14-90 days (73% [59-82%]), 91-180 days (71% [60-80%]), and 181-274 days (70% [54-81%]) postvaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18-65%) among immunocompetent patients. Conclusions . The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months postvaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients.

Updated Multiple Linear Regression Models for Predicting Chronic Aluminum Toxicity to Freshwater Aquatic Organisms and Developing Water Quality Guidelines.

Multiple linear regression (MLR) models for predicting chronic aluminum toxicity to a cladoceran (Ceriodaphnia dubia) and a fish (Pimephales promelas) as a function of 3 toxicity-modifying factors (TMFs)-dissolved organic carbon (DOC), pH, and hardness-have been published previously. However, the range over which data for these TMFs were available was somewhat limited. To address this limitation, additional chronic toxicity tests with these species were subsequently conducted to expand the DOC range up to 12 mg/L, the pH range up to 8.7, and the hardness range up to 428 mg/L. The additional toxicity data were used to update the chronic MLR models. The adjusted R2 for the C. dubia 20% effect concentration (EC20) model increased from 0.71 to 0.92 with the additional toxicity data, and the predicted R2 increased from 0.57 to 0.89. For P. promelas, the adjusted R2 increased from 0.87 to 0.92 and the predicted R2 increased from 0.72 to 0.87. The high predicted R2 relative to the adjusted R2 indicates that the models for both species are not overly parameterized. When data for C. dubia and P. promelas were pooled, the adjusted R2 values were comparable to the species-specific models (0.90 and 0.88 for C. dubia and P. promelas, respectively). This indicates that chronic aluminum EC20s for C. dubia and P. promelas respond similarly to variation in DOC, pH, and hardness. Overall, the pooled model predicted EC20s that were within a factor of 2 of observed in 100% of the C. dubia tests and 94% of the P. promelas tests. Environ Toxicol Chem 2020;39:1724-1736. © 2020 SETAC.

Phototoxicity Assessments of Field Sites in Barataria Bay, Louisiana, USA, and Heavily Weathered Macondo Crude Oil: 4 Years after the Deepwater Horizon Oil Spill.

The Deepwater Horizon oil spill resulted in the release of large amounts of crude oil into waters of the Gulf of Mexico (USA). A significant portion of the oil reached coastal waters and shorelines where aquatic organisms reside. Four years after the spill, oil remains in small quantities along the coast. Given the high volume of oil coupled with the high ultraviolet light intensities of the Gulf of Mexico, continued polycyclic aromatic hydrocarbon phototoxicity may be occurring in the Gulf region. The objective of the present study was to determine the potential for phototoxicity at 5 field sites (oiled, remediated, and unoiled) in Barataria Bay (LA, USA) to caged mysid shrimp and sheepshead minnows and to evaluate the phototoxic potential of field-collected oil water accommodated fractions (WAFs). Water chemistries were similar between field-collected oil WAFs and ambient waters, excluding the most oiled field site. Field bioassays indicated no phototoxic risk of heavily weathered crude oil under the highly turbid conditions present during the study. Laboratory WAFs of field-collected oil resulted in phototoxicity to mysid shrimp, suggesting a potential for phototoxicity of heavily weathered crude oil remaining in the Gulf of Mexico. Environ Toxicol Chem 2019;38:1811-1819. © 2019 SETAC.

Determination of Bioavailable Aluminum in Natural Waters in the Presence of Suspended Solids.

Analyses of natural waters frequently show elevated levels of total aluminum (Al) attributable to acid extraction of Al from the total suspended solids (TSS) minerals. Hence, there is a need for an analytical method that measures only bioavailable Al. Natural waters high in TSS were collected to study the chronic effects of Al on Ceriodaphnia dubia. In the collected waters TSS ranged from 30 to 411 mg/L; total Al concentrations ranged from 2.0 to 44.8 mg/L. The TSS in natural waters inhibited reproduction of C. dubia up to 40% in comparison to the same filtered waters. This inhibition did not correlate with the concentration of TSS or total Al; it was attributed to nutritional deficiency and was prevented by increasing the food supply. To demonstrate that toxicity can be measured in natural waters, samples with elevated TSS were spiked with soluble Al, and survival and reproduction were measured in chronic studies performed at pH 6.3 and 8.0. To properly characterize the Al concentrations in the toxicity studies, a method was needed that could discriminate bioavailable Al from mineral forms of Al. An extraction method at pH 4 for bioavailable Al was developed and evaluated using C. dubia chronic toxicity studies in the presence of TSS. It is concluded that the proposed method is better able to discriminate chronic toxicity effects attributable to bioavailable Al from mineralized nontoxic forms of Al compared with existing methods using total or total recoverable Al (i.e., extraction at pH ≤ 1.5). We propose that this new method be used when assessing the potential for Al in natural surface waters to cause toxicity. Environ Toxicol Chem 2019;38:1668-1681. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

Photo-enhanced toxicity of undispersed and dispersed weathered Macondo crude oil to Pacific (Crassostrea gigas) and eastern oyster (Crassostrea virginica) larvae.

During the Deepwater Horizon oil spill rapid natural weathering of Macondo crude oil occurred during the transport of oil to coastal areas. In response to the DWH incident, dispersant was applied to Macondo crude oil to reduce the movement of oil to coastal regions. This study aimed to assess the narcotic and phototoxicity of water-accommodated fractions (WAFs) of weathered Macondo crude oil, and chemically-enhanced WAFs of Corexit 9500 to Pacific (Crassostrea gigas) and eastern (Crassostrea virginica) oyster larvae. Phototoxic effects were observed for larval Pacific oysters exposed to combinations of oil and dispersant, but not for oil alone. Phototoxic effects were observed for larval eastern oysters exposed to oil alone and combinations of oil and dispersant. Corexit 9500 did not exhibit phototoxicity but resulted in significant narcotic toxicity for Pacific oysters. Oyster larvae may have experienced reduced survival and/or abnormal development if reproduction coincided with exposures to oil or dispersant.

Development and application of a biotic ligand model for predicting the chronic toxicity of dissolved and precipitated aluminum to aquatic organisms.

Aluminum (Al) toxicity to aquatic organisms is strongly affected by water chemistry. Toxicity-modifying factors such as pH, dissolved organic carbon (DOC), hardness, and temperature have a large impact on the bioavailability and toxicity of Al to aquatic organisms. The importance of water chemistry on the bioavailability and toxicity of Al suggests that interactions between Al and chemical constituents in exposures to aquatic organisms can affect the form and reactivity of Al, thereby altering the extent to which it interacts with biological membranes. These types of interactions have previously been observed in the toxicity data for other metals, which have been well described by the biotic ligand model (BLM) framework. In BLM applications to other metals (including cadmium, cobalt, copper, lead, nickel, silver, and zinc), these interactions have focused on dissolved metal. A review of Al toxicity data shows that concentrations of Al that cause toxicity are frequently in excess of solubility limitations. Aluminum solubility is strongly pH dependent, with a solubility minimum near pH 6 and increasing at both lower and higher pH values. For the Al BLM, the mechanistic framework has been extended to consider toxicity resulting from a combination of dissolved and precipitated Al to recognize the solubility limitation. The resulting model can effectively predict toxicity to fish, invertebrates, and algae over a wide range of conditions. Environ Toxicol Chem 2018;37:70-79. © 2017 SETAC.

Evaluating the effects of pH, hardness, and dissolved organic carbon on the toxicity of aluminum to freshwater aquatic organisms under circumneutral conditions.

Although it is well known that increasing water hardness and dissolved organic carbon (DOC) concentrations mitigate the toxicity of aluminum (Al) to freshwater organisms in acidic water (i.e., pH < 6), these effects are less well characterized in natural waters at circumneutral pHs for which most aquatic life regulatory protection criteria apply (i.e., pH 6-8). The evaluation of Al toxicity under varying pH conditions may also be confounded by the presence of Al hydroxides and freshly precipitated Al in newly prepared test solutions. Aging and filtration of test solutions were found to greatly reduce toxicity, suggesting that toxicity from transient forms of Al could be minimized and that precipitated Al hydroxides contribute significantly to Al toxicity under circumneutral conditions, rather than dissolved or monomeric forms. Increasing pH, hardness, and DOC were found to have a protective effect against Al toxicity for fish (Pimephales promelas) and invertebrates (Ceriodaphnia dubia, Daphnia magna). For algae (Pseudokirchneriella subcapitata), the protective effects of increased hardness were only apparent at pH 6, less so at pH 7, and at pH 8, increased hardness appeared to increase the sensitivity of algae to Al. The results support the need for water quality-based aquatic life protection criteria for Al, rather than fixed value criteria, as being a more accurate predictor of Al toxicity in natural waters. Environ Toxicol Chem 2018;37:49-60. © 2017 SETAC.

Chronic toxicity of aluminum, at a pH of 6, to freshwater organisms: Empirical data for the development of international regulatory standards/criteria.

The chemistry, bioavailability, and toxicity of aluminum (Al) in the aquatic environment are complex and affected by a wide range of water quality characteristics (including pH, hardness, and dissolved organic carbon). Data gaps in Al ecotoxicology exist for pH ranges representative of natural surface waters (pH 6-8). To address these gaps, a series of chronic toxicity tests were performed at pH 6 with 8 freshwater species, including 2 fish (Pimephales promelas and Danio rerio), an oligochaete (Aeolosoma sp.), a rotifer (Brachionus calyciflorus), a snail (Lymnaea stagnalis), an amphipod (Hyalella azteca), a midge (Chironomus riparius), and an aquatic plant (Lemna minor). The 10% effect concentrations (EC10s) ranged from 98 µg total Al/L for D. rerio to 2175 µg total Al/L for L. minor. From these data and additional published data, species-sensitivity distributions (SSDs) were developed to derive concentrations protective of 95% of tested species (i.e., 50% lower confidence limit of a 5th percentile hazard concentration [HC5-50]). A generic HC5-50 (not adjusted for bioavailability) of 74.4 µg total Al/L was estimated using the SSD. An Al-specific biotic ligand model (BLM) was used to develop SSDs normalized for bioavailability based on site-specific water quality characteristics. Normalized HC5-50s ranged from 93.7 to 534 µg total Al/L for waters representing a range of European ecoregions, whereas a chronic HC5 calculated using US Environmental Protection Agency aquatic life criteria methods (i.e., a continuous criterion concentration [CCC]) was 125 µg total Al/L when normalized to Lake Superior water in the United States. The HC5-50 and CCC values for site-specific waters other than those in the present study can be obtained using the Al BLM. Environ Toxicol Chem 2018;37:36-48. © 2017 SETAC.

Acute and chronic toxicity of aluminum to a unionid mussel (Lampsilis siliquoidea) and an amphipod (Hyalella azteca) in water-only exposures.

The US Environmental Protection Agency (USEPA) is reviewing the protectiveness of the national ambient water quality criteria (WQC) for aluminum (Al) and compiling a toxicity data set to update the WQC. Freshwater mussels are one of the most imperiled groups of animals in the world, but little is known about their sensitivity to Al. The objective of the present study was to evaluate acute 96-h and chronic 28-d toxicity of Al to a unionid mussel (Lampsilis siliquoidea) and a commonly tested amphipod (Hyalella azteca) at a pH of 6 and water hardness of 100 mg/L as CaCO3 . The acute 50% effect concentration (EC50) for survival of both species was >6200 µg total Al/L. The EC50 was greater than all acute values in the USEPA acute Al data set for freshwater species at a pH range of 5.0 to <6.5 and hardness normalized to 100 mg/L, indicating that the mussel and amphipod were insensitive to Al in acute exposures. The chronic 20% effect concentration (EC20) based on dry weight was 163 µg total Al/L for the mussel and 409 µg total Al/L for the amphipod. Addition of the EC20s to the USEPA chronic Al data set for pH 5.0 to <6.5 would rank the mussel (L. siliquoidea) as the fourth most sensitive species and the amphipod (H. azteca) as the fifth most sensitive species, indicating the 2 species were sensitive to Al in chronic exposures. The USEPA-proposed acute and chronic WQC for Al would adequately protect the mussel and amphipod tested; however, inclusion of the chronic data from the present study and recalculation of the chronic criterion would likely lower the proposed chronic criterion. Environ Toxicol Chem 2018;37:61-69. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Chronic effects of non-weathered and weathered crude oil and dispersant associated with the Deepwater Horizon incident on development of larvae of the eastern oyster, Crassostrea virginica.

The present study examined the effects of chronic exposure of eastern oyster (Crassostrea virginica) larvae to the water-accommodated fractions of fresh and weathered oils collected from the Deepwater Horizon incident, with and without additions of the dispersant Corexit 9500A, as well as to solutions of Corexit alone. Both shell growth of larvae exposed to test materials for a period of 10 d and larval settlement after 28 d of exposure were the most sensitive endpoints, with the 10-d growth endpoint being less variable among replicates. Growth and settlement endpoints were more sensitive than larval survival and normal development after 10 d and 28 d. Acute-to-chronic ratios calculated in the present study suggest that acute toxicities of oils and dispersant for oysters are not predictive of chronic effect levels for growth and settlement; therefore, chronic bioassays are necessary to assess these sublethal effects, in addition to standard 48-h acute toxicity tests. Comparison of 10% effective concentration (EC10) values for chronic 10-d growth and 28-d settlement endpoints with concentrations of total polycyclic aromatic hydrocarbons and dipropylene glycol n-butyl ether (a marker for Corexit) in seawater samples, collected during and after the Deepwater Horizon incident, indicated it was unlikely that elevated concentrations of water-soluble fractions of oil and dispersant in the nearshore environment had significant adverse effects on the growth and settlement of eastern oyster larvae. Environ Toxicol Chem 2016;35:2029-2040. © 2016 SETAC.

Acute effects of non-weathered and weathered crude oil and dispersant associated with the Deepwater Horizon incident on the development of marine bivalve and echinoderm larvae.

Acute toxicity tests (48-96-h duration) were conducted with larvae of 2 echinoderm species (Strongylocentrotus purpuratus and Dendraster excentricus) and 4 bivalve mollusk species (Crassostrea virginica, Crassostrea gigas, Mytilus galloprovincialis, and Mercenaria mercenaria). Developing larvae were exposed to water-accommodated fractions (WAFs) and chemically enhanced water-accommodated fractions (CEWAFs) of fresh and weathered oils collected from the Gulf of Mexico during the Deepwater Horizon incident. The WAFs (oils alone), CEWAFs (oils plus Corexit 9500A dispersant), and WAFs of Corexit alone were prepared using low-energy mixing. The WAFs of weathered oils had no effect on survival and development of echinoderm and bivalve larvae, whereas WAFs of fresh oils showed adverse effects on larval development. Similar toxicities were observed for weathered oil CEWAFs and WAFs prepared with Corexit alone for oyster (C. gigas and C. virginica) larvae, which were the most sensitive of the tested invertebrate species to Corexit. Mean 10% effective concentration values for total polycyclic aromatic hydrocarbons and dipropylene glycol n-butyl ether (a marker for Corexit) in the present study were higher than all concentrations reported in nearshore field samples collected during and after the Deepwater Horizon incident. The results suggest that water-soluble fractions of weathered oils and Corexit dispersant associated with the Deepwater Horizon incident had limited, if any, acute impacts on nearshore larvae of eastern oysters and clams, as well as other organisms with similar sensitivities to those of test species in the present study; however, exposure to sediments and long-term effects were not evaluated. Environ Toxicol Chem 2016;35:2016-2028. © 2016 SETAC.

The interactive toxicity of cadmium, copper, and zinc to Ceriodaphnia dubia and rainbow trout (Oncorhynchus mykiss).

Traditionally, aquatic toxicity studies examine the toxicity of a single chemical to an organism. Organisms in nature, however, may be exposed to multiple toxicants. Given this is a more realistic exposure scenario in situ, the authors sought to understand the interactive toxicity of multiple metals to aquatic organisms. The authors performed a series of studies using equitoxic mixtures of cadmium, copper, and zinc to 2 aquatic organisms, rainbow trout (Oncorhynchus mykiss) and the waterflea, Ceriodaphnia dubia. Single metal toxicity tests were conducted to determine the acute median lethal concentration (LC50) values for O. mykiss and short-term, chronic median effective concentration (EC50) values for C. dubia. All 3 metals were then combined in equitoxic concentrations for subsequent mixture studies using a toxic unit (TU) approach (i.e., 1 TU = EC50 or LC50). For C. dubia, the mixture study showed greater-than-additive effects in hard water (TU-based EC50 = 0.74 TU), but less-than-additive effects in soft water (TU-based EC50 = 1.93 TU). The mixture effects for O. mykiss showed less-than-additive effects in both hard and soft waters, with TU-based LC50 values of 2.33 total TU and 2.22 total TU, respectively. These data are useful in helping understand metal mixture toxicity in aquatic systems and indicate that although in most situations the assumption of additivity of metal mixture toxicity is valid, under certain conditions it may not be sufficiently protective.

Quantitative risk model for polycyclic aromatic hydrocarbon photoinduced toxicity in Pacific herring following the Exxon Valdez oil spill.

Phototoxicity occurs when exposure to ultraviolet radiation increases the toxicity of certain contaminants, including polycyclic aromatic hydrocarbons (PAHs). This study aimed to (1) develop a quantitative model to predict the risk of PAH phototoxicity to fish, (2) assess the predictive value of the model, and (3) estimate the risk of PAH phototoxicity to larval and young of year Pacific herring (Clupea pallasi) following the Exxon Valdez oil spill (EVOS) in Prince William Sound, Alaska. The model, in which median lethal times (LT50 values) are estimated from whole-body phototoxic PAH concentrations and ultraviolet A (UVA) exposure, was constructed from previously reported PAH phototoxicity data. The predictive value of this model was confirmed by the overlap of model-predicted and experimentally derived LT50 values. The model, along with UVA characterization data, was used to generate estimates for depths of de minimiz risk for PAH phototoxicity in young herring in 2003/2004 and immediately following the 1989 EVOS, assuming average and worst case conditions. Depths of de minimiz risk were estimated to be between 0 and 2 m deep when worst case UVA and PAH conditions were considered. A post hoc assessment determined that <1% of the young herring population would have been present at depths associated with significant risk of PAH phototoxicity in 2003/2004 and 1989.

Quantifying the concentration of crude oil microdroplets in oil-water preparations.

Dissolved constituents of crude oil, particularly polycyclic aromatic hydrocarbons (PAHs), can contribute substantially to the toxicity of aquatic organisms. Measured aqueous concentrations of high-molecular weight PAHs (e.g., chrysenes, benzo[a]pyrene) as well as long-chain aliphatic hydrocarbons can exceed the theoretical solubility of these sparingly soluble compounds. This is attributed to the presence of a "microdroplet" or colloidal oil phase. It is important to be able to quantify the dissolved fraction of these compounds in oil-in-water preparations that are commonly used in toxicity assays because the interpretation of test results often assumes that the compounds are dissolved. A method is presented to determine the microdroplet contribution in crude oil-in-water preparations using a comparison of predicted and measured aqueous concentrations. Measured concentrations are reproduced in the model by including both microdroplets and dissolved constituents of petroleum hydrocarbons. Microdroplets were found in all oil-water preparation data sets analyzed. Estimated microdroplet oil concentrations typically ranged from 10 to 700 µg oil/L water. The fraction of dissolved individual petroleum hydrocarbons ranges from 1.0 for highly soluble compounds (e.g., benzene, toluene, ethylbenzene, and xylene) to far less than 0.1 for sparingly soluble compounds (e.g., chrysenes) depending on the microdroplet oil concentration. The presence of these microdroplets complicates the interpretation of toxicity test data because they may exert an additional toxic effect due to a change in the exposure profile. The implications of the droplet model on toxicity are also discussed in terms of both dissolved hydrocarbons and microdroplets.

Cross-species extrapolation of chronic nickel Biotic Ligand Models.

The use of Biotic Ligand Models (BLMs) to normalize metal ecotoxicity data and predict effects in non-BLM organisms should be supported by quantitative evidence. This study determined the ability of chronic nickel BLMs developed for the cladocera Daphnia magna and Ceriodaphnia dubia to predict chronic nickel toxicity to three invertebrates for which no specific BLMs were developed. Those invertebrates were the snail Lymnaea stagnalis, the insect Chironomus tentans, and the rotifer Brachionus calyciflorus. Similarly, we also determined the ability of chronic nickel BLMs developed for the alga Pseudokirchneriella subcapitata and the terrestrial vascular plant Hordeum vulgare to predict chronic nickel toxicity to the aquatic vascular plant Lemna minor. Chronic nickel toxicity to the three invertebrates and the aquatic plant were measured in five natural waters that varied in pH, Ca, Mg, and dissolved organic carbon (DOC), which are known to affect chronic nickel toxicity and are the important input variables for the chronic nickel BLMs. Nickel toxicity to the three invertebrates varied considerably among the test waters, i.e., a 14-fold variation of EC50s in L. stagnalis, a 3-fold variation in EC20s in C. tentans, and a 10-fold variation in EC20s in B. calyciflorus, but the cladoceran BLMs were able to predict nickel effect concentrations within a factor of two. Nickel toxicity (EC50s) to L. minor varied by 6-fold among the test waters. Although the P. subcapitata and H. vulgare BLMs offered reasonable predictions of nickel EC50s to L. minor, the D. magna and C. dubia BLM showed better predictions. Our results confirm the influence of site-specific pH, hardness, and DOC on chronic nickel toxicity to aquatic organisms, and support the use of chronic nickel BLMs to manage this influence through normalizations of ecotoxicity data.

Structural basis for ESCRT-III protein autoinhibition.

Endosomal sorting complexes required for transport-III (ESCRT-III) subunits cycle between two states: soluble monomers and higher-order assemblies that bind and remodel membranes during endosomal vesicle formation, midbody abscission and enveloped virus budding. Here we show that the N-terminal core domains of increased sodium tolerance-1 (IST1) and charged multivesicular body protein-3 (CHMP3) form equivalent four-helix bundles, revealing that IST1 is a previously unrecognized ESCRT-III family member. IST1 and its ESCRT-III binding partner, CHMP1B, both form higher-order helical structures in vitro, and IST1-CHMP1 interactions are required for abscission. The IST1 and CHMP3 structures also reveal that equivalent downstream alpha5 helices can fold back against the core domains. Mutations within the CHMP3 core-alpha5 interface stimulate the protein's in vitro assembly and HIV-inhibition activities, indicating that dissociation of the autoinhibitory alpha5 helix from the core activates ESCRT-III proteins for assembly at membranes.