Ecological Risk Analysis for Benzalkonium Chloride, Benzethonium Chloride, and Chloroxylenol in US Disinfecting and Sanitizing Products.

Use of three topical antiseptic compounds-benzalkonium chloride (BAC), benzethonium chloride (BZT), and chloroxylenol (PCMX)-has recently increased because of the phaseout of other antimicrobial ingredients (such as triclosan) in soaps and other disinfecting and sanitizing products. Further, use of sanitizing products in general increased during the coronavirus (COVID-19) pandemic. We assessed the environmental safety of BAC, BZT, and PCMX based on best available environmental fate and effects data from the scientific literature and privately held sources. The ecological exposure assessment focused on aquatic systems receiving effluent from wastewater-treatment plants (WWTPs) and terrestrial systems receiving land-applied WWTP biosolids. Recent exposure levels were characterized based on environmental monitoring data supplemented by modeling, while future exposures were modeled based on a hypothetical triclosan replacement scenario. Hazard profiles were developed based on acute and chronic studies examining toxicity to aquatic life (fish, invertebrates, algae, vascular plants) and terrestrial endpoints (plants, soil invertebrates, and microbial functions related to soil fertility). Risks to higher trophic levels were not assessed because these compounds are not appreciably bioaccumulative. The risk analysis indicated that neither BZT nor PCMX in any exposure media is likely to cause adverse ecological effects under the exposure scenarios assessed in the present study. Under these scenarios, total BAC exposures are at least three times less than estimated effect thresholds, while margins of safety for freely dissolved BAC are estimated to be greater than an order of magnitude. Because the modeling did not specifically account for COVID-19 pandemic-related usage, further environmental monitoring is anticipated to understand potential changes in environmental exposures as a result of increased antiseptic use. The analysis presented provides a framework to interpret future antiseptic monitoring results, including monitoring parameters and modeling approaches to address bioavailability of the chemicals of interest. Environ Toxicol Chem 2022;41:3095-3115. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Adsorption isotherms of Polyquaternium-10 polymers by activated sludge solids.

Polymeric quaternary ammonium salts (polyquaternium-10 polymers, PQ-10) are extensively used as components of hair care products, lotions, and makeup and, therefore, are present in domestic sewage. Adsorption of these polymers by activated sludge was assessed to evaluate their removal by a commonly used wastewater treatment process. Activated sludge solids (ASS) were dosed with PQ-10 polymers with relatively high molecular mass (JR-125 and JR-30 M) and relatively low molecular mass (LR-400 and LR-30 M) and equilibrated for 2 h at 20 ± 2 °C. After equilibration, the vessels with the mixtures were centrifuged and the supernatants were analyzed with a phenol method. The relationships between dosed amounts and equilibrium concentrations in the aqueous phase (dose-response curves) for each tested polymer indicated that at relatively low dosing solution concentrations were negligible ("total adsorption" region of the dose-response curve). Light absorbance of the samples prepared for determination of polymer concentration using a phenol method within this region was close to the absorbance of the blank (0 µg (a.i.)/mL) or below absorbance of the blank, resulting in calculated concentrations apparently below zero. At some level of dosing, a subsequent increase in polymer dosage resulted in a quantifiable increase in solution concentration ("solution concentration rising" region). The relationships between concentrations of the polymers in the aqueous phase and concentrations of adsorbed polymers (adsorption isotherms) were non-linear. The ability of activated sludge solids to bind tested polymers may be characterized by apparent "threshold values" of the loading for each polymer. Below the "threshold value," solution concentration of the polymer is close to zero and above this value it becomes measurable. "Threshold loading" for all polymers was from 50 to 100 mg (a.i.)/g, far above concentrations of these compounds expected to be present in the sewage.

Environmental risk assessment of polycarboxylate polymers used in cleaning products in the United States.

Polycarboxylate polymers have been common components of consumer and institutional cleaning products for decades. With interest heightened in the potential environmental impact of polymers, the American Cleaning Institute, the industry trade association of the cleaning products industry in the United States, is reassessing the state of the science regarding the environmental safety of polymers in cleaning products. In this case study, acrylic acid homopolymers and acrylic acid-maleic acid copolymers are evaluated using historical ecotoxicity data that have been reported over the past three decades. The evaluation includes an environmental exposure assessment that is based on recent information regarding the occurrence of those ingredients in cleaning products and market sales data for cleaning products sold in the United States. The ecotoxicity of polycarboxylate polymers is generally low. Consequently, the potential environmental risks associated with their use in cleaning products in the United States are low even when applying very conservative assumptions to the environmental exposure assessment. In addition, there are recent supporting conclusions from assessments by the governments of Australia and Canada that polycarboxylate polymers are polymers of low concern, and the U.S. Environmental Protection Agency has included a number of polycarboxylate polymers among the ingredients on its Safer Chemical Ingredients List based on their low hazard profile.

Polymers Used in US Household Cleaning Products: Assessment of Data Availability for Ecological Risk Assessment.

The purpose of this study was to identify, characterize, and assess data needs for ecological risk of household cleaning product polymers currently being used in the United States (US). Because of their range in properties and functions, polymers are used in a wide variety of household cleaning products, including fabric, dish, and hard surface cleaners. Understanding their potential environmental impact is essential for good ingredient and product stewardship. The household cleaning product polymers were first identified using several databases. Of the 185 polymers initially identified, 120 were eliminated from the list because they did not fit the definition of a polymer, were not well defined (e.g., no Chemical Abstracts Service [CAS] or trade name only), or were not in current use. Forty-seven of the remaining polymers had either adequate environmental fate and hazard data and/or sufficient data for conducting a comprehensive ecological risk assessment and were determined to be of low concern by either the United States Environmental Protection Agency (USEPA), the European Chemicals Agency (ECHA), and/or the Human and Environmental Risk Assessment (HERA) Project. The remaining 18 polymers were determined to need further review because of a lack of publicly available information for conducting ecological risk assessments. Additional data for these 18 polymers could be obtained by accessing privately held data, conducting laboratory tests on their fate and effects in aquatic environments, or by conducting read-across of similar structured polymers. These steps can be utilized by industry to determine where best to dedicate future environmental stewardship efforts. Integr Environ Assess Manag 2019;15:621-632. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Quantifying the benefits of using read-across and in silico techniques to fulfill hazard data requirements for chemical categories.

Substantial benefits are realized through the use of read-across and in silico techniques to fill data gaps for structurally similar substances. Considerable experience in applying these techniques was gained under two voluntary high production volume (HPV) chemical programs - the International Council of Chemical Associations' (ICCA) Cooperative Chemicals Assessment Programme (with the cooperation of the Organization of Economic Cooperation and Development) and the U.S. Environmental Protection Agency's HPV Challenge Program. These programs led to the compilation and public availability of baseline sets of health and environmental effects data for thousands of chemicals. The American Cleaning Institute's (ACI) contribution to these national and global efforts included the compilation of these datasets for 261 substances. Chemicals that have structural similarities are likely to have similar environmental fate, physical-chemical and toxicological properties, which was confirmed by examining available data from across the range of substances within categories of structurally similar HPV chemicals. These similarities allowed the utilization of read-across, trend analysis techniques and qualitative structure activity relationship ((Q)SAR) tools to fill data gaps. This paper presents the first quantification of actual benefits resulting from avoided testing through the use of read-across and in silico tools. Specifically, in the evaluation of these 261 noted substances, the use of 100,000-150,000 test animals and the expenditures of $50,000,000 to $70,000,000 (US) were avoided.

Environmental Safety of the Use of Major Surfactant Classes in North America.

This paper brings together over 250 published and unpublished studies on the environmental properties, fate, and toxicity of the four major, high-volume surfactant classes and relevant feedstocks. The surfactants and feedstocks covered include alcohol sulfate or alcohol sulfate (AS), alcohol ethoxysulfate (AES), linear alkylbenzene sulfonate (LAS), alcohol ethoxylate (AE), and long-chain alcohol (LCOH). These chemicals are used in a wide range of personal care and cleaning products. To date, this is the most comprehensive report on these substance's chemical structures, use, and volume information, physical/chemical properties, environmental fate properties such as biodegradation and sorption, monitoring studies through sewers, wastewater treatment plants and eventual release to the environment, aquatic and sediment toxicity, and bioaccumulation information. These data are used to illustrate the process for conducting both prospective and retrospective risk assessments for large-volume chemicals and categories of chemicals with wide dispersive use. Prospective risk assessments of AS, AES, AE, LAS, and LCOH demonstrate that these substances, although used in very high volume and widely released to the aquatic environment, have no adverse impact on the aquatic or sediment environments at current levels of use. The retrospective risk assessments of these same substances have clearly demonstrated that the conclusions of the prospective risk assessments are valid and confirm that these substances do not pose a risk to the aquatic or sediment environments. This paper also highlights the many years of research that the surfactant and cleaning products industry has supported, as part of their environmental sustainability commitment, to improve environmental tools, approaches, and develop innovative methods appropriate to address environmental properties of personal care and cleaning product chemicals, many of which have become approved international standard methods.

Occurrence and risk screening of alcohol ethoxylate surfactants in three U.S. river sediments associated with wastewater treatment plants.

Alcohol ethoxylates (AE) are high production volume (HPV) chemicals globally used in detergent and personal care products and are truly a work-horse for the household and personal care industries. Commercial AE generally consist of a mixture of several homologues of varying carbon chain length and degree of ethoxylation. Homologues that are not ethoxylated are also known as aliphatic alcohols or simply fatty alcohols (FA). This group of homologues represents a special interest in the context of environmental risk, as these are also abundant and ubiquitous naturally occurring compounds (e.g. animal fats and in human feces). Hence, in a risk assessment one needs to distinguish between the natural (background) concentrations and the added contribution from anthropogenic activities. We conducted a weight-of-evidence risk assessment in three streams, documenting the exposure and predicted risk, and compared these to the habitat and in situ biota. We found that the parameters (e.g., habitat quality and total perturbations hereunder total suspended solids (TSS) and other abiotic and biotic stressors) contributed to the abundance of biota rather than the predicted risk from AE and FA. Moreover, the documented natural de novo synthesis and rapid degradation of FA highlight the need to carefully consider the procedures for environmental risk assessment of naturally occurring compounds such as FA, e.g. in line with the added risk concept known from metal risk assessment.

Relationships between benthic macroinvertebrate community structure and geospatial habitat, in-stream water chemistry, and surfactants in the effluent-dominated Trinity River, Texas, USA.

Over the past 20 years, benthic macroinvertebrate community structure studies have been conducted on the upper Trinity River, Texas, USA, which is dominated by municipal wastewater treatment plant (WWTP) and industrial effluents. The Trinity River is located in the Dallas-Fort Worth metropolitan area, and is the most highly populated and industrialized watershed in Texas. As such, the Trinity River represents a near-worst-case scenario to examine the environmental effects of domestic-municipal and industrial effluents on aquatic life. A 1987 to 1988 study concluded that many stretches of the river supported a diverse benthic community structure; however, a decline in taxa richness occurred immediately downstream of WWTPs. A 2005 study designed to parallel the 1987 to 1988 efforts evaluated how changes in water quality, habitat, and increased urbanization impacted benthic community structure. Physicochemical measurements, habitat quality, geospatial variables, and benthic macroinvertebrates were collected from 10 sites. Surfactants were measured and toxic units (TUs) were calculated for surface water and pore water as indicators of domestic/household use of cleaning products. Total TUs indicated a low potential for biological impacts. Toxic unit distribution was not dependent on WWTP location and did not correlate with any benthic variable. Eight environmental parameters were determined to be useful for predicting changes in benthic macroinvertebrate community structure: surfactant surface water TUs (SWTU), in-stream habitat cover, and surface water total organic carbon were the top three parameters. Abundance, taxa richness, and taxa similarity in 2005 had increased since the earlier study throughout the immediate vicinity of the metropolitan area.

Environmental risk assessment of hydrotropes in the United States, Europe, and Australia.

An environmental assessment of hydrotropes was conducted under the Organisation for Economic Co-operation and Development (OECD) Screening Information Data Sets (SIDS) for High Production Volume (HPV) Program via the Global International Council of Chemical Associations (ICCA) Hydrotropes Consortium. The assessment and its conclusions were presented at a meeting of the OECD member countries in Washington, DC in 2005. The SIDS Initial Assessment Report (SIAR) was accepted by the membership. Their conclusion was "The chemicals in this [hydrotropes] category are of low priority for further work because of their low hazard profile." Hydrotropes are used to solubilize the water-insoluble ingredients of cleaning and personal care products including, for example, powder and liquid laundry detergents, hard-surface cleaners, machine dishwashing rinse aids, hand dishwashing liquids, body washes, shampoos, hair conditioners, and liquid hand and face soaps. Global production equals approximately 46 500 metric tons, a little more than half of which is used in the United States. The 8 chemicals accounted for in the "hydrotropes category" include ammonium, Ca, K, and Na salts that are described by 10 Chemical Abstract Service (CAS) registration numbers. The 8 chemical entities are generally comparable and predictable in their chemical behavior and that measured and/or modeled data for members from one subgroup can be applied to other subgroups and to the hydrotropes category as a whole. The assessment is based on a search for and evaluation of available data on physical­chemical properties, biodegradability, removal by wastewater treatment, and aquatic toxicity. Reliable ecotoxicity and environmental fate data were found for selected members of the category. Partitioning, once released into the environment, and exposure in surface waters were modeled for consumer use and manufacturing scenarios relevant to the United States, Europe, and Australia. The models indicate 99+% of the hydrotropes will partition to water. Furthermore, given the low potential for hydrotropes reaching the terrestrial environment and their lack of persistence or bioaccumulation, the focus of the assessment is on the aquatic environment, specifically the water compartment. Aquatic risks were assessed in each scenario using what is referred to as the PEC/PNEC ratio. The modeled predicted environmental concentration (PEC), accounting for volume released and wastewater treatment, is divided by the predicted no effect concentration (PNEC) derived from the aquatic toxicity tests. The closest a predicted environmental concentration came to the toxicity threshold is 0.125 (or 12.5% of the no effect concentration) and that is for a hypothetical manufacturing facility that produces the entire annual volume of hydrotropes and discharges to a small (10%ile) stream under low flow (7Q10) conditions. PEC/PNEC ratios were considerably smaller for consumer use scenarios. The ratios were 0.0002 for a low flow (7Q10) stream scenario in the United States, 0.026 to 0.089 for regional and local water bodies, respectively, in Europe, and 0.004 to 0.036 for oceans and rivers, respectively, in Australia. In conclusion, aquatic hazard levels are not expected to be reached under exaggerated conditions of manufacture or normal consumer use of hydrotropes. Hydrotropes are neither persistent nor bioaccumulative in the environment.

High production volume chemical amine oxides [C8-C20] category environmental risk assessment.

An environmental assessment of amine oxides has been conducted under the OECD SIDS High Production Volume (HPV) Program via the Global International Council of Chemical Associations (ICCA) Amine Oxides Consortium. Amine oxides are primarily used in conjunction with surfactants in cleaning and personal care products. Given the lack of persistence or bioaccumulation, and the low likelihood of these chemicals partitioning to soil, the focus of the environmental assessment is on the aquatic environment. In the United States, the E-FAST model is used to estimate effluent concentrations in the United States from manufacturing facilities and from municipal facilities resulting from consumer product uses. Reasonable worst-case ratios of predicted environmental concentration (PEC) to predicted no effect concentration (PNEC) range from 0.04 to 0.003, demonstrating that these chemicals are a low risk to the environment.

Human health risk assessment of long chain alcohols.

Representative chemicals from the long chain alcohols category have been extensively tested to define their toxicological hazard properties. These chemicals show low acute and repeat dose toxicity with high-dose effects (if any) related to minimal liver toxicity. These chemicals do not show evidence of activity in genetic toxicity tests or to the reproductive system or the developing organism. These chemicals also are not sensitizers. Irritation is dependant on chain length; generally, alcohols in the range C(6-)C(11) are considered as irritant, intermediate chain lengths (C(12-)C(16)) alcohols are considered to be mild irritants and chain lengths of C(18) and above are considered non-irritants. These chemicals are broadly used across the consumer products industry with highest per person consumer exposures resulting from use in personal care products. Margins of exposure adequate for the protection of human health are documented for the uses of these chemicals.

Environmental properties of long chain alcohols. Part 1: Physicochemical, environmental fate and acute aquatic toxicity properties.

This paper summarises the physicochemical, biodegradation and acute aquatic ecotoxicity properties of long chain aliphatic alcohols. Properties of pure compounds are shown to follow somewhat predictable trends, which are amenable to estimation by quantitative structure-activity relationships ((Q)SARs). This allows predictions of data relating to human and environmental safety profiles and patterns. These alcohols have been shown to be rapidly degradable under standard conditions up to C(18). Furthermore, evidence suggests that longer chain lengths are also rapidly biodegradable. While logK(ow) values suggest possible bioaccumulation potential, available data suggest that these substances are not as bioaccumulative as estimations would predict. For acute aquatic toxicity, solubility limits the possibility of effects being appropriately observed and become increasingly challenging above C(12). Further, a model has been developed for multi-component mixtures which give an excellent account of aquatic ecotoxicity allowing for the prediction of acute effects of un-tested mixtures.

An overview of hazard and risk assessment of the OECD high production volume chemical category--long chain alcohols [C(6)-C(22)] (LCOH).

This review summarizes the findings of the assessment report for the category, long chain alcohols (LCOH) with a carbon chain length range of C(6)-C(22) covering 30 substances, and >1.5million tonnes/year consumed globally. The category was evaluated under the Organization for Economic Co-operation and Development (OECD) high production volume chemicals program in 2006. The main findings of the assessment include: (1) no unacceptable human or environmental risks were identified; (2) these materials are rapidly and readily biodegradable; (3) a parabolic relationship was demonstrated between carbon chain length and acute and chronic aquatic toxicity; (4) category-specific (quantitative) structure-activity relationships were developed enabling prediction of properties across the entire category; (5) LCOH occur naturally in the environment in an equilibrium between synthesis and degradation; (6) industry coming together and sharing resources results in minimizing the need for additional animal tests, produces cost savings, and increases scientific quality of the assessment.

Occurrence and weight-of-evidence risk assessment of alkyl sulfates, alkyl ethoxysulfates, and linear alkylbenzene sulfonates (LAS) in river water and sediments.

Alkyl sulfates (AS), alkyl ethoxysulfates (AES) and linear alkyl benzene sulfonates (LAS) are all High Production Volume (HPV) and 'down-the-drain' chemicals used globally in detergent and personal care products, resulting in low levels ultimately released to the environment via wastewater effluent. Due to their surfactant properties, they preferentially sorb to sediments. Hence, assessment of their levels and potential perturbations on benthos are of interest. The relative levels of AS/AES decreased with distance from the wastewater treatment plant outfall. However, this was not evident for LAS. Short chained AES and especially AS dominated the homologue distribution for AES. There were no evident patterns in LAS homologue distribution. The overall mean margin of exposure (MoE) for AS/AES and LAS is approximately 40 (range: 3 to 100) suggesting no noteworthy perturbation on biota. The findings in this study are in concordance with previous preliminary hazard screening. Comparative sediment contamination analyses principally based on Chapman and Anderson [Chapman PM, Anderson, J. A decision-making framework for sediment contamination. Integr Environ Assess Mana. 2005; 1: 163-173.] and the U.S. Environmental Protection Agency RAPID assessment methods [USEPA. Rapid bioassessment protocols for use in wadeable streams and rivers: Periphyton, benthic, macroinvertebrates, and fish. 1999. Second Edition. U.S. Environmental Protection Agency Office of Water, Washington, D.C. EPA 841-B-99-002.] did not reveal significant correlations between the surfactant concentrations and ecological status of the sampling locations. Several Lines of Evidence (LoE) of the Weight-of-Evidence (WoE) lead to the conclusion of low aquatic risk associated to the monitored compounds.

Effect of different resuscitation strategies on neutrophil activation in a swine model of hemorrhagic shock.

UNLABELLED: Activated neutrophils play a pivotal role in resuscitation injury. The strategies used for resuscitation (types of fluids and methods of administration) can affect the degree of neutrophil activation. The aim of this study was to test the commonly available resuscitation fluids in a large animal model of hemorrhagic shock to determine the strategy associated with the least degree of neutrophil activation. METHODS: Female swine (n=63, weight 45-60 kg) were anesthetized using isoflurane and catheters were placed for hemodynamic monitoring. After 120 min, they were subjected to a volume controlled hemorrhage (28 ml/kg) over 15 min, kept in shock for 60 min, and then resuscitated. The resuscitation groups were as follows: (1) anesthesia only (n=5); (2) hemorrhage, sham resuscitation (n=5); (3) LR-fast rate 3x blood loss (n=6); (4) LR slow rate-3x blood loss (n=6); (5) LR low volume-1x blood loss (n=6); (6) Dextran 40-1x blood loss (n=6); (7) 6% hetastarch-1x blood loss (n=6); (8) 5% albumin-1x blood loss (n=6); (9) 25% albumin-1/5x blood loss (n=6); (10) whole blood resuscitation-1x blood loss (n=6); (11) 7.5% hypertonic saline (HTS)-0.3x blood loss (n=5). Resuscitation fluids were infused over 1 h in all groups except group 4 (LR slow rate, which was over 3 h). Animals were observed for 180 min following the resuscitation period. Neutrophil oxidative burst activity was determined in whole blood using flow cytometery. RESULTS: Animals resuscitated with dextran and hetastarch showed significantly (P<0.05) higher neutrophil burst activity. Resuscitation with LR also caused neutrophil activation (P<0.05), and the highest degree of activation was seen when a large volume of LR was given at a fast rate (group 8). However, all LR infusion protocols were associated with significant neutrophil activation compared with anesthesia (group 1) or sham resuscitation (group 2). No significant activation was seen in the animals resuscitated with albumin or fresh whole blood. CONCLUSION: Artificial colloids and LR (independent of rate or volume of infusion) caused significant neutrophil activation, which was not seen with albumin and whole blood resuscitation. These findings suggest that the type of resuscitation fluid and method of infusion can influence neutrophil function.

Human polymorphonuclear cell death after exposure to resuscitation fluids in vitro: apoptosis versus necrosis.

BACKGROUND: Resuscitation fluids can have variable effects on key functions of circulating polymorphonuclear neutrophils (PMNs) such as oxidative burst, chemotaxis, and bacterial killing. We hypothesized that choice of resuscitation fluids will also affect the rate of PMN apoptosis. To test this, we studied cellular death (apoptosis and necrosis) in human PMNs after brief exposure to different hypertonic and isotonic fluids. METHODS: Blood from 12 volunteers was incubated for 1 hour at 37 degrees C in normal saline, 6.0% dextran-70, 7.5% hypertonic saline, and 7.5% hypertonic saline with 6% dextran-70. Isolated PMNs were double labeled with fluorescein-Annexin V and propidium iodide, and apoptosis and necrosis were measured using flow cytometry. Caspase activation was also detected with flow cytometry using pan-caspase inhibitor (carbobenzoxy-valyl-alanyl-aspartyl-fluoromethylketone) in non-isolated whole blood samples to determine apoptosis. Finally, cDNA macroarrays were used to evaluate the expression of 23 genes involved in the regulation of cell cycling and apoptosis. RESULTS: Exposure to hypertonic fluids (hypertonic saline and 7.5% hypertonic saline with 6% dextran-70) significantly (p < 0.05) increased necrosis in isolated PMNs. In whole blood samples, PMNs exposed to dextran demonstrated significant apoptosis as evidenced by increased caspase activation. Dextran was the only fluid that affected leukocyte gene expression, inducing significant up-regulation of Rb gene transcription. CONCLUSION: Hypertonic fluids and dextran decrease human polymorphonuclear cell survival through necrotic and apoptotic pathways, respectively.

Learning and memory is preserved after induced asanguineous hyperkalemic hypothermic arrest in a swine model of traumatic exsanguination.

BACKGROUND: Induced asanguineous hypothermic metabolic arrest (suspended animation) could provide valuable time to repair major vascular injuries if safely induced in patients with trauma. We report a novel method of doing this in a swine model of uncontrolled lethal hemorrhage (ULH) that resulted in preservation of learning ability and memory. METHODS: Yorkshire swine (100 to 125 lb) underwent ULH before rapid intra-aortic infusion of a hypothermic (4 degrees C), hyperkalemic (70 mEq/L) organ preservation solution by a left thoracotomy. Cooling continued until core temperature reached 10 degrees C, and this was maintained for 60 minutes using low-flow cardiopulmonary bypass. Vascular injuries were repaired during this state of suspended animation, which was then reversed, and the animals were observed for 6 weeks. Cognitive functions were tested by training animals to retrieve food from color-coded boxes. Postoperatively, the ability to remember this task and a 75-point objective neurologic scale were used to test neurologic function. In experiment I, ULH was caused by lacerating thoracic aorta (n = 9). Five preoperatively untrained animals were trained to perform the task and compared with control animals (n = 15), and 4 preoperatively trained animals were tested for memory retention postoperatively. In experiment II, ULH was induced by creating an iliac artery and vein injury (n = 15). Animals were kept in shock for 15, 30, and 60 minutes before the induction of hypothermia. RESULTS: In experiment I, surviving animals (7/9) were neurologically intact, and their capacity to learn new skills was no different than for control animals. All pretrained animals demonstrated complete memory retention. In experiment II, survival with 15, 30, and 60 minutes of shock were 80%, 60%, and 80%, respectively. All animals (except 1) in the 60-minute group were neurologically intact and displayed normal learning capacity. CONCLUSIONS: Induction of hypothermic metabolic arrest (by thoracotomy) for repair of complex traumatic injuries is feasible with preservation of normal neurologic function, even after extended periods of shock from an intra-abdominal source of uncontrolled hemorrhage.

Effects of lactated Ringer's solutions on human leukocytes.

BACKGROUND: The standard lactated Ringer's (LR) solution contains racemic lactate, an equal mixture of D(-)- and L(+)-isomers. The aim of this study was to investigate whether racemic LR solution (containing both isomers, dl-LR) differs from LR containing L-isomer only (L-LR). METHODS: Blood from 20 volunteers was incubated for 30 minutes with lactated Ringer's solutions containing the DL- or L-form of lactate, Hank's balanced salt solution, normal saline, and ketone Ringer's (lactate replaced with ketone bodies). Neutrophil "oxidative burst" was measured using flow cytometry. Gene expression of 23 genes associated with leukocyte function was determined with cDNA array technique. The arraying procedure was repeated four times to obtain four sets of data. RESULTS: Compared with the L-LR and ketone Ringer's, DL-LR causes an increased production of reactive oxygen species by neutrophils and affects expression of leukocyte genes known to be involved in inflammation, cell migration, and apoptosis. CONCLUSION: Lactated Ringer's solution in commonly used formulation (racemic mixture, DL-LR) influences neutrophil function and leukocyte gene expression.