Application of the Target Lipid Model and Passive Samplers to Characterize the Toxicity of Bioavailable Organics in Oil Sands Process-Affected Water.

Oil sand operations in Alberta, Canada will eventually include returning treated process-affected waters to the environment. Organic constituents in oil sand process-affected water (OSPW) represent complex mixtures of nonionic and ionic (e.g., naphthenic acids) compounds, and compositions can vary spatially and temporally, which has impeded development of water quality benchmarks. To address this challenge, it was hypothesized that solid phase microextraction fibers coated with polydimethylsiloxane (PDMS) could be used as a biomimetic extraction (BE) to measure bioavailable organics in OSPW. Organic constituents of OSPW were assumed to contribute additively to toxicity, and partitioning to PDMS was assumed to be predictive of accumulation in target lipids, which were the presumed site of action. This method was tested using toxicity data for individual model compounds, defined mixtures, and organic mixtures extracted from OSPW. Toxicity was correlated with BE data, which supports the use of this method in hazard assessments of acute lethality to aquatic organisms. A species sensitivity distribution (SSD), based on target lipid model and BE values, was similar to SSDs based on residues in tissues for both nonionic and ionic organics. BE was shown to be an analytical tool that accounts for bioaccumulation of organic compound mixtures from which toxicity can be predicted, with the potential to aid in the development of water quality guidelines.

Macrophytes are highly sensitive to the herbicide diquat dibromide in test systems of varying complexity.

The herbicide diquat dibromide is used in North America to manage nuisance macrophytes. However, its effect on native macrophytes is less clear and it could cause indirect effects on other aquatic biota. This study determined the sensitivity of both native and non-native macrophytes grown in test systems with varying complexity to diquat dibromide applied directly to water following label directions. In an outdoor mesocosm experiment and single species greenhouse concentration-response tests, Elodea canadensis Michx., Myriophyllum spicatum L., Ceratophyllum demersum L. and Hydrocharis morsus-ranae L. were exposed to a range of diquat dibromide concentrations (4.7 - 1153 µg/L), corresponding to 0.4 - 100% of the recommended label rate of the formulated product. The mesocosm experiment contained all four plant taxa in the same system along with caged amphipods (Hyalella azteca Saus.), tadpoles (Lithobates pipiens Schreber), phytoplankton and periphyton; however, this study focuses on the macrophytes only. In both test systems, severe direct effects of diquat dibromide on macrophytes were detected, with almost 100% mortality of all macrophytes in both test systems at 74 µg/L. The most sensitive species in the single species tests, E. canadensis, showed almost 100% mortality at concentrations below the HPLC-based method detection limit of 5 µg/L. Effects occurred very rapidly and showed no difference in severity between native and non-native macrophytes or complexity of test systems. These results suggest that diquat dibromide could be applied at a considerably lower label rate, depending on the characteristics of the waterbody, while still achieving effective control of nuisance macrophytes.

Bioaccumulation of sediment-associated substituted phenylamine antioxidants in Tubifex tubifex and Lampsilis siliquoidea.

Substituted phenylamine antioxidants (SPAs) are additives in a variety of commercial polymers (e.g., lubricants, plastics, etc.). Based on their physicochemical properties, if SPAs were to enter an aquatic system, they would likely partition into sediment and have the capacity to bioaccumulate in biota. This study investigated the potential of four sediment-associated SPAs, diphenylamine (DPA), N-phenyl-1-naphthalene (PNA), N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (DPPDA), and 4,4'-methylene-bis[N-sec-butylaniline] (MBA) to accumulate in the tissues of freshwater mussels (Lampsilis siliquoidea) and oligochaete worms (Tubifex tubifex). Mussels and worms were exposed to sediment spiked with individual SPAs for 28 d. The concentration of SPAs was measured in the gill, gonad, and remaining viscera of the mussels and entire body of the worms. The majority of biota-sediment accumulation factors (28-d BSAFs) for the different tissues of mussels were < 1. The highest concentrations of SPAs were consistently observed in the gill tissue of mussels relative to the gonad and viscera. The 28-d BSAFs for DPPDA and MBA for worms were < 1, and for DPA and PNA, they ranged from 0.38-2.13 and 1.54-33.24, respectively. The higher 28-d BSAFs observed for worms compared to mussels were likely because worms are endobenthic and feed on sediment-associated organic matter. PNA and DPPDA have similar octanol-water partition coefficients (Kow) but greater 28-d BSAFs were observed for PNA compared to DPPDA for both species. This observation provides evidence that biota may be able to metabolize and/or excrete SPAs with similar physicochemical properties at considerably different rates. The 28-d BSAFs observed for sediment-associated SPAs are lower than those typically required for a chemical to be classified as bioaccumulative.

Optimizing Sex Ratios of Hyalella azteca to Reduce Variability in Reproduction and Improve Reproductive Toxicity Test Methods.

Standard toxicological test methods with Hyalella azteca incorporate both lethal and sublethal (growth, reproduction) endpoints, although lethal endpoints are often favored in routine testing. However, sublethal endpoints are important to consider because they are ecologically relevant and are often more sensitive than lethality. It is difficult to achieve robust data for reproduction in H. azteca because high biological variability is associated with reproductive yield, likely due to complex interactions in mate selection, which can add to the variability in brood sizes that females produce. In addition, effects on reproduction often co-occur with effects on growth, making it difficult to differentiate effects on growth from those on reproduction in standard tests initiated with juveniles. The present study characterized the reproductive capacity of H. azteca by investigating the role of sex ratios in reproductive yield. Experiments were initiated in the absence of toxicants with sexually mature (6-8-week-old) individuals that were placed in different female-to-male ratios (1:1, 2:3, 3:2, and 7:3). Reproduction was monitored during weekly static renewals for 7 weeks. The results indicated that a higher female:male ratio (seven females to three males) improved reproductive success and lowered biological variability in reproduction. In addition, the body lengths and weights of newly mature amphipods were used to create a size distribution to aid in the identification of small female amphipods. Based on the results of our study, a novel reproductive toxicity test method is proposed that begins with sexually mature amphipods in a ratio of seven females to three males to minimize reproductive variability in amphipods and to enable a more effective assessment of contaminants using reproduction as a highly sensitive endpoint. However, evaluation of this novel method with toxicants is needed to demonstrate that results are comparable to standard methods. Environ Toxicol Chem 2024;43:712-722. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Bioaccumulation of sediment-associated dinonylnaphthalene sulfonates in the freshwater mussel Lampsilis siliquoidea and oligochaete Tubifex tubifex.

Naphthalene sulfonic acids (NSAs) are used primarily as additives in a wide range of industrial products (e.g., rubber materials, coatings, sealants, fuels, paints). Based on modeled physicochemical properties, NSAs would likely partition into sediments or the tissues of biota in an aquatic system. This study examined the potential for three NSAs, dinonylnaphthalene disulfonic acid (DNDS), barium dinonylnaphthalene sulfonate (BaDNS), and calcium dinonylnaphthalene sulfonate (CaDNS), to accumulate in the tissue of a freshwater mussel (Lampsilis siliquoidea) and oligochaete worm (Tubifex tubifex). The ability of L. siliquoidea to depurate accumulated chemical was also assessed. Mussels were exposed via sand spiked with CaDNS for 25 d, and then transferred to clean water where their ability to depurate the chemical over an additional 28 d was monitored. Worms were exposed to each of the three NSAs via spiked sediment for 28 d. NSA concentrations were measured separately in gill, foot, and remaining soft tissues (viscera) for mussels and in whole body tissue samples of worms. For L. siliquoidea, the largest concentration of CaDNS was measured in the gill tissue; once removed from CaDNS exposure, mussels were able to depurate up to 87% of the CaDNS from their tissues in 28 days. The biota-sediment accumulation factors (28-d BSAFs) for T. tubifex were 2.8-5.2, 0.53-0.76, and 0.83-1.11 for DNDS, BaDNS, and CaDNS, respectively. For mussel gill and viscera, BCFK values were 14.07 and 16.39, respectively. When BAFKs were calculated using the concentration of CaDNS in sand, they were 1.11 and 1.29 for mussel gill and viscera, respectively. These values are much lower than what would be necessary to classify this chemical as bioaccumulative; however, the BSAFs for DNDS in T. tubifex indicated a potential biomagnification concern if this compound were to occur in the aquatic environment.

The influence of organic carbon on the toxicity of sediment-associated dinonylnaphthalene sulfonic acids to the benthic invertebrates Tubifex tubifex and Hyalella azteca.

Naphthalene sulfonic acids (NSAs) are used extensively in industrial applications as dispersants in dyes, rubbers, and pesticides, and as anti-corrosive agents in coatings, gels, and sealants. This study examined the toxicity of three NSA congeners, barium dinonylnaphthalene sulfonate (BaDNS), calcium dinonylnaphthalene sulfonate (CaDNS), and dinonylnaphthalene disulfonic acid (DNDS), to two benthic species, Tubifex tubifex and Hyalella azteca. Two substrates with different levels of organic carbon (sediment [2%] and sand [0%]) were used in toxicity tests. Juvenile production was the most sensitive endpoint for T. tubifex: the 28-d EC50s were <18.2, 22.2, and 64.0 µg/g dw in sand and 281.3, 361.6, and 218.9 µg/g dw in sediment for BaDNS, CaDNS, and DNDS, respectively. The 28-d LC50s for H. azteca were similar among compounds: 115.3, 82.1, and 49.0 µg/g dry weight (dw) in sand, and 627.3, 757.9, and >188.5 µg/g dw in sediment, for BaDNS, CaDNS, and DNDS, respectively. However, when LC50s were estimated based on concentrations of NSAs measured in overlying water (which can be an important route of exposure for H. azteca), BaDNS and CaDNS were 3-4 orders of magnitude more toxic than DNDS. The NSAs examined were >3-fold more toxic when present in substrates with no organic carbon (e.g., sand) for all H. azteca endpoints where LC/EC50s could be calculated and for sublethal endpoints for T. tubifex. The organic carbon content of the sediment appears to have acted as a sink and reduced NSA toxicity by decreasing bioavailability. Environmental sediment samples were collected from 12 river sites across southern Ontario. The maximum concentration of CaDNS observed in sediment collected from this region was 2.8 µg/g dw in sediment with 2% organic carbon; 100-fold lower than the lowest EC10 in the current study.

Toxicity of dinonylnaphthalene sulfonates to Pimephales promelas and epibenthic invertebrates.

Dinonylnaphthalene sulfonic acids (NSAs) are high production volume chemicals that are used primarily as additives in a wide range of industrial products (i.e., coatings, sealants, fuels, metal-extractants, paints, rubber materials). This study examined the effect of three NSA congeners on freshwater organisms: barium dinonylnaphthalene sulfonate (BaDNS), calcium dinonylnaphthalene sulfonate (CaDNS), and dinonylnaphthalene disulfonic acid (DNDS). Chronic effects were characterized by exposing fertilized fathead minnow eggs to sediment-associated NSAs and measuring various developmental and growth endpoints for 21 d. No effects in hatch success and larval growth were observed when fathead minnow eggs were exposed to CaDNS and DNDS concentrations up to 246 and 798 µg/g dry weight, respectively, in spiked sediment (~2% organic carbon). However, when NSAs were associated with substrate containing no organic carbon (sand), EC50s for fathead minnow hatch success, larval growth, biomass production, and overall survival were 58.3, 18.8, 15.5, and 13.8 µg/L, respectively, for CaDNS. Acute effect characterization was also conducted in water-only exposures for the three NSA congeners using the freshwater amphipod Hyalella azteca, the pulmonate snail Planorbella pilsbryi, and larval freshwater mussels Lampsilis cardium and Lampsilis siliquoidea. The sulfonate salts (BaDNS and CaDNS) were significantly more acutely toxic to all tested invertebrates in the water-only exposures, with LC50s ranging from 0.47 to 12.1 µg/L, compared to DNDS (LC50s ≥ 98.2 µg/L). This is the first study to provide empirical data on the aquatic toxicity of three NSA congeners.

Assessment of Sublethal Effects of Neonicotinoid Insecticides on the Life-History Traits of 2 Frog Species.

Neonicotinoid insecticides are used extensively in agriculture and, as a consequence, are now detectable in nearby aquatic environments. Few studies have evaluated the effects of neonicotinoids on amphibians in these aquatic environments. In the present study, we examined the effects of 2 commercial formulations of neonicotinoids (active ingredients clothianidin and thiamethoxam) on survival and life-history traits of wood frogs (Lithobates sylvaticus) and northern leopard frogs (Lithobates pipiens). We used artificial pond mesocosms to assess the effects of these neonicotinoids, at nominal concentrations of 2.5 and 250 µg/L, on amphibian larval development through metamorphosis. We found no differences between controls and neonicotinoid exposure for any of the endpoints assessed for either wood frogs or leopard frogs. The present study suggests that concentrations meeting or exceeding observed levels of clothianidin and thiamethoxam in surface waters will not directly affect metamorphosis in 2 amphibians. Environ Toxicol Chem 2019;38:1967-1977. © 2019 SETAC.

The toxicity of organic fractions from aged oil sands process-affected water to aquatic species.

The process of surface mining and extracting bitumen from oil sand produces large quantities of tailings and oil sands process-affected water (OSPW). The industry is currently storing OSPW on-site while investigating strategies for their detoxification. One such strategy relies on the biodegradation of organic compounds by indigenous microbes, resulting in aged tailings waters with reduced toxicity. This study assessed the toxicity of OSPW aged statically for approximately 18 years. Dissolved organics in aged OSPW were fractionated using a preparative solid-phase extraction method that generated three organic fractions (F1-F3) of increasing polarity. Eight aquatic species from different trophic levels were exposed to whole OSPW (WW) and the derived OSPW organic fractions to assess toxicity: Pimephales promelas, Oryzias latipes, Vibrio fischeri, Daphnia magna, Lampsilis cardium, Hyalella azteca, Ceriodaphnia dubia, and Hexagenia spp. Broad comparisons revealed that P. promelas and H. azteca were most sensitive to dissolved organics within aged OSPW, while WW was most toxic to L. cardium and H. azteca. Three cases of possible contaminant interactions occurred within whole OSPW treatments, as toxicity was higher than organic fractions for H. azteca and L. cardium, and lower for P. promelas. As such, the drivers of toxicity appeared to be dependent on the species exposed. Of the organic fractions assessed, F3 (most polar) was the most toxic overall while F2 (intermediate polarity) displayed little toxicity to all species evaluated. This presents strong evidence that classical mono-carboxylic naphthenic acids, mostly present in F1 (least polar), are not primarily responsible for the toxicity in aged tailings. The current study indicates that although the aged tailings source (≥18 years) did not display acute toxicity to the majority of organisms assessed, inorganic components and polyoxygenated organics may pose a persistent concern to some aquatic organisms.

Variation in the toxicity of sediment-associated substituted phenylamine antioxidants to an epibenthic (Hyalella azteca) and endobenthic (Tubifex tubifex) invertebrate.

Substituted phenylamine antioxidants (SPAs) are produced in relatively high volumes and used in a range of applications (e.g., rubber, polyurethane); however, little is known about their toxicity to aquatic biota. Therefore, current study examined the effects of chronic exposure (28 d) to four sediment-associated SPAs on epibenthic (Hyalella azteca) and endobenthic (Tubifex tubifex) organisms. In addition, acute (96-h), water-only exposures were conducted with H. azteca. Mortality, growth and biomass production were assessed in juvenile H. azteca exposed to diphenylamine (DPA), N-phenyl-1-napthylamine (PNA), N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (DPPDA), or 4,4'-methylene-bis[N-sec-butylaniline] (MBA). Mortality of adult T. tubifex and reproduction were assessed following exposure to the four SPAs. The 96-h LC50s for juvenile H. azteca were 1443, 109, 250, and >22 µg/L and 28-d LC50s were 22, 99, 135, and >403 µg/g dry weight (dw) for DPA, PNA, DPPDA, and MBA, respectively. Reproductive endpoints for T. tubifex (EC50s for production of juveniles > 500 µm: 15, 9, 4, 3.6 µg/g dw, for DPA, PNA, DPPDA, and MBA, respectively) were an order of magnitude more sensitive than endpoints for juvenile H. azteca and mortality of adult worms. The variation in toxicity across the four SPAs was likely related to the bioavailability of the sediment-associated chemicals, which was determined by the chemical properties of the SPAs (e.g., solubility in water, Koc). The variation in the sensitivity between the two species was likely due to differences in the magnitude of exposure, which is a function of the life histories of the epibenthic amphipod and the endobenthic worm. The data generated from this study will support effect characterization for ecological risk assessment.

Effect of substituted phenylamine antioxidants on three life stages of the freshwater mussel Lampsilis siliquoidea.

Substituted phenylamines (SPAs) are incorporated into a variety of consumer products (e.g., polymers, lubricants) in order to increase the lifespan of the products by acting as a primary antioxidant. Based on their physicochemical properties, if SPAs were to enter the aquatic environment, they would likely partition into sediment. No studies to date have investigated the effect of sediment-associated SPAs on aquatic organisms. The current study examined the effect of four SPAs (diphenylamine (DPA); N-phenyl-1-napthylamine (PNA); N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (DPPDA); 4,4'-methylene-bis[N-sec-butylaniline] (MBA)) on three different life stages of the freshwater mussel, Lampsilis siliquoidea. The viability of larvae (glochidia) of L. siliquoidea and Lampsilis fasciola was assessed after 48 h of exposure to SPAs in water. The 48-h EC50s for glochidia viability of L. siliquoidea were 5951, 606, 439, and 258 µg/L for DPA, PNA, DPPDA, and MBA, respectively, and 7946, 591, 137, and 47 µg/L, respectively, for L. fasciola. Juvenile (7-15 months) and adult L. siliquoidea were exposed to sediment-associated SPAs for 28 d. LC50s for juvenile mussels were 18, 55, 62, and 109 µg/g dry weight (dw) of sediment for DPA, PNA, DPPDA, and MBA, respectively. Adult mussels were exposed to sub-lethal concentrations of sediment-associated SPAs in order to investigate reactive oxygen species (ROS), lipid peroxidation and total glutathione in the gill, gonad, and digestive gland tissue, and viability and DNA damage in hemocytes. No significant concentration-dependent trend in any of these biochemical and cellular endpoints relative to the concentration of sediment-associated SPAs was observed in any tissues. Investigations into the concentration of SPAs in the aquatic environment are required before a conclusion can be made on whether these compounds pose a hazard to the different life stages of freshwater mussels.

Sensitivity of the early-life stages of freshwater mollusks to neonicotinoid and butenolide insecticides.

Neonicotinoid insecticides can be transported from agricultural fields, where they are used as foliar sprays or seed treatments, to surface waters by surface or sub-surface runoff. Few studies have investigated the toxicity of neonicotinoid or the related butenolide insecticides to freshwater mollusk species. The current study examined the effect of neonicotinoid and butenolide exposures to the early-life stages of the ramshorn snail, Planorbella pilsbryi, and the wavy-rayed lampmussel, Lampsilis fasciola. Juvenile P. pilsbryi were exposed to imidacloprid, clothianidin, or thiamethoxam for 7 or 28 d and mortality, growth, and biomass production were measured. The viability of larval (glochidia) L. fasciola was monitored during a 48 h exposure to six neonicotinoids (imidacloprid, thiamethoxam, clothianidin, acetamiprid, thiacloprid, or dinotefuran), or a butenolide (flupyradifurone). The 7-d LC50s of P. pilsbryi for imidacloprid, clothianidin, and thiamethoxam were ≥4000 µg/L and the 28-d LC50s were ≥182 µg/L. Growth and biomass production were considerably more sensitive endpoints than mortality with EC50s ranging from 33.2 to 122.0 µg/L. The 48-h LC50s for the viability of glochidia were ≥456 µg/L for all seven insecticides tested. Our data indicate that neonicotinoid and butenolide insecticides pose less of a hazard with respect to mortality of the two species of mollusk compared to the potential hazard to other non-target aquatic insects.

A convenient and efficient moldable dressing for skin grafts.

In this paper we present our positive experience with use of Aquaplast thermoplastic as a tie-down dressing for securing and maintaining skin grafts in good position against their nutrient recipient beds. This unique polymer is safe to use, simple to apply, and maintains uniform pressure across the entire surface of the skin graft, no matter how contoured the shape of the anatomical region.

Causes of toxicity to Hyalella azteca in a stormwater management facility receiving highway runoff and snowmelt. Part I: polycyclic aromatic hydrocarbons and metals.

The Terraview-Willowfield Stormwater Management Facility (TWSMF) receives inputs of multiple contaminants, including metals, polycyclic aromatic hydrocarbons (PAHs), road salt, and nutrients, via highway and residential runoff. Contaminant concentrations in runoff are seasonally dependent, and are typically high in early spring, coinciding with the snowmelt. In order to investigate the seasonal fluctuations of contaminant loading and related changes in toxicity to benthic invertebrates, overlying water and sediment samples were collected in the fall and spring, reflecting low and high contaminant loading, respectively, and four-week sediment toxicity tests were conducted with Hyalella azteca. The effects of metals and PAHs are discussed here; the effects of salts, nutrients, and water quality are discussed in a companion paper. Survival and growth of Hyalella after exposure to fall samples were variable: survival was significantly reduced (64-74% of controls) at three out of four sites, but there were no significant growth effects. More dramatic effects were observed after Hyalella were exposed to spring samples: survival was significantly reduced at the two sites furthest downstream (0-75% of controls), and growth was significantly lower in four out of five sites when comparing Hyalella exposed to site sediment with overlying site water versus site sediment with overlying control water. These seasonal changes in toxicity were not related to metals or PAHs: 1. levels of bioavailable metals were below those expected to cause toxicity, and 2. levels of PAHs in sediment were lowest at sites with the greatest toxicity and highest in water and sediment at sites with no toxicity. Although not associated with toxicity, some metals and PAHs exceeded probable and severe effect levels, and could be a cause for concern if contaminant bioavailability changes. Toxicity in the TWSMF appeared to be primarily associated with water-borne contaminants. The cause(s) of these effects are discussed in our companion manuscript.

Causes of toxicity to Hyalella azteca in a stormwater management facility receiving highway runoff and snowmelt. Part II: salts, nutrients, and water quality.

The Terraview-Willowfield Stormwater Management Facility (TWSMF) features a tandem of stormwater management ponds, which receive inputs of multiple contaminants from highway and residential runoff. Previous research determined that benthic communities in the ponds were impacted by poor habitat quality, due to elevated sediment concentrations of metals and polycyclic aromatic hydrocarbons (PAHS), and salinity in the overlying water, but did not address seasonal changes, including those caused by the influx of contaminants with the snowmelt. In order to address this issue, water and sediment samples were collected from the TWSMF during the fall and spring, and four-week sediment toxicity tests were conducted with Hyalella azteca. The effects of metals and PAHs are discussed in a companion paper; the effects of road salt, nutrients, and water quality are discussed here. After exposure to fall samples, survival of Hyalella was reduced (64-74% of controls) at three out of four sites, but growth was not negatively affected. After exposure to spring samples, survival was 0-75% of controls at the two sites furthest downstream, and growth was significantly lower in four out of five sites when comparing Hyalella exposed to site water overlying site sediment versus control water overlying site sediment. Toxicity appeared to be related to chloride concentrations: little or no toxicity occurred in fall samples (200 mg Cl(-)/L), and significant effects on survival and growth occurred in spring samples above 1550 mg Cl(-)/L and 380 mg Cl(-)/L, respectively. Sodium chloride toxicity tests showed similar results: four-week LC50s and EC25s (growth) were 1200 and 420 mg Cl(-)/L, respectively. Although water quality and nutrients were associated with effects observed in the TWSMF, chloride from road salt was the primary cause of toxicity in this study. Chloride persists during much of the year at concentrations representing a significant threat to benthic communities in the TWSMF.

The portable Glostavent: a new anaesthetic machine for use in difficult situations.

A portable version of the Glostavent anaesthetic machine is described in which recent developments in draw-over technology are incorporated into a traditional draw-over anaesthetic system. The additional features include a more efficient reservoir and an improved vaporiser which have enhanced the performance and versatility. The portable Glostavent weighs less than 10 kg and is transported in a container the size of a small suitcase. It can be used to provide inhalational anaesthesia safely and economically in situations where there are no support facilities. It is ideal for use in battlefield or disaster situations and in isolated hospitals in disadvantaged regions of the world.

Emerging differences between 5-HT3 receptor antagonists.

A brief review is presented of some recently described 5-HT3 receptor antagonists. These antagonists are primarily targeted for use as anti-emetics. However, evidence is emerging that there are differences in their basic pharmacology. This evidence is reviewed in terms of the selectivity of the antagonists in binding studies and also of their efficacy in emesis and gastric emptying. The possibility that these differences may translate into meaningful clinical differences between the available 5-HT3 receptor antagonists in their use as anti-emetics is also discussed.

Ventilation strategies affect surfactant aggregate conversion in acute lung injury.

This study evaluated the effects of varying tidal volumes (VT) and positive end-expiratory pressure (PEEP) levels on surfactant aggregate conversion and lung function in an animal model of lung injury induced by N-nitroso-N-methylurethane. Lung-injured adult rabbits were initially ventilated using a VT of 10 ml/kg (VT10), a respiratory rate of 30 breaths/min (RR30), and a PEEP of 3.5 cm H2O. A trace dose of radiolabeled rabbit large surfactant aggregates was instilled after the onset of ventilation, and animals were then ventilated at different ventilator settings for 1 h. Ventilation strategies involving a lower VT (VT5, RR60) resulted in significantly superior oxygenation and lower surfactant aggregate conversion rates than strategies involving a higher VT ([VT10, RR30], [VT15, RR20], p < 0.05). Increasing the PEEP level to 8.0 cm H2O improved oxygenation, but it was sustained only with a low VT (VT5, RR60), and deteriorated with a high VT (VT10, RR30). Varying VT but not PEEP levels resulted in significant changes in surfactant aggregate conversion. We conclude that increased surfactant aggregate conversion resulting from suboptimal ventilation of injured lungs may play an important role in the pathophysiology of ventilation-induced lung dysfunction in acute lung injury.

The radioimmunoassay of buprenorphine.

Antisera to buprenorphine were obtained in rabbits immunised with 3-0-carboxymethylbuprenorphine and N-hemisuccinyl-norbuprenorphine conjugated to bovine serum albumin. Using the latter antiserum and tritium labelled buprenorphine a radioimmunoassay have good accuracy and precision was developed for concentrations as low as 50 picograms in 1 ml of plasma. The N-hemisuccinyl antiserum crossreacted with norbuprenorphine, and the 3-0-glucuronide conjugate with the 3-0-carboxymethyl antiserum. Cross-reactivity of both antisera to other pharmacologically related compounds was negligible. The assay was employed to determine plasma buprenorphine concentration following its parenteral administration to dog and man.

Effects of ventilation strategies on the efficacy of exogenous surfactant therapy in a rabbit model of acute lung injury.

We evaluated the effects of various ventilation strategies on the efficacy of exogenous surfactant therapy in lung-injured adult rabbits. Lung injury was induced by repetitive whole-lung saline lavage followed by mechanical ventilation. Three hours after the final lavage, 100 mg lipid/kg bovine lipid extract surfactant was instilled. After confirmation of similar responses to exogenous surfactant, animals were then randomized to one of four ventilation groups; (1) Normal tidal volume (VT) (5 cm H2O): VT = 10 ml/kg, respiratory rate (RR) = 30/min, positive end-expiratory pressure (PEEP) = 5 cm H2O; (2) Normal VT (9 cm H2O): VT = 10 ml/kg, RR = 30/min, PEEP = 9 cm H2O; (3) Low VT (5 cm H2O): VT = 5 ml/kg, RR = 60/min, PEEP = 5 cm H2O; (4) Low VT (9 cm H2O): VT = 5 ml/kg, RR = 60/min, PEEP = 9 cm H2O. Animals were ventilated for an additional 3 h and then killed, and lung lavage fluid was analyzed. Animals ventilated with the low-VT modes (Low VT [5 cm H2O] and Low VT [9 cm H2O]) had higher PaO2 values (430 +/- 7 mm Hg and 425 +/- 18 mm Hg versus 328 +/- 13 mm Hg) and higher percentages of surfactant in large aggregate forms (83 +/- 2% and 82 +/- 2% versus 67 +/- 4%) at 3 h after treatment than did the Normal VT (5 cm H2O) group (p < 0.05). Increasing the PEEP level was beneficial for a short period after surfactant administration to maintain oxygenation, but did not affect exogenous surfactant aggregate conversion. We speculate that ventilation strategies resulting in low exogenous surfactant aggregate conversion will result in superior physiologic responses to exogenous surfactant.