bluuebunny/crossref_metadata_2025 huggingface dataset:
Lycomimodes, a new generic replacement name for preoccupied Lycomimus Lawrence and Slipinski, 2013 (Insecta: Coleoptera: Ptilodactylidae) non Melzer, 1931 (Insecta: Coleoptera: Cerambycidae)
Authors: LAWRENCE JOHN F. , SLIPINSKI ADAM
Published: September 2013

The generic name Lycomimus (L. bejsaki Lawrence and Slipinski 2013, by original designation) was proposed by Lawrence and Slipinski (2013, p. 71) for a new coleopteran genus from northern New South Wales and southern Queensland, Australia. However, this name is already preoccupied by Lycomimus Melzer (1931, p. 11). To resolve homonomy, in accordance with the International Code of Zoological Nomenclature, Lycomimodes nom. nov. (type species Lycomimus bejsaki Lawrence and Slipinski, 2013) is here proposed as a replacement name for Lycomimus Lawrence and Slipinski 2013, non Melzer. The name is derived from the beetle family Lycidae, the Greek mimos, actor and the Greek suffix odes denoting likeness; the gender is masculine.
A new species of Lappodiamesa Serra-Tosio (Diptera: Chironomidae: Diamesinae) from the Russian Far East, with a key to known species of the genus
Authors: MAKARCHENKO EUGENYI A. , MAKARCHENKO MARINA A.
Published: September 2013

The male, pupa, and larva of a new species, Lappodiamesa omelkoi, from the Russian Far East are described and figured. Keys to males, pupae, and fourth-instar larvae of known species of the genus are presented.
Elucidating Article 45.6 of the International Code of Zoological Nomenclature: A dichotomous key for the determination of subspecific or infrasubspecific rank
Authors: LINGAFELTER STEVEN W. , NEARNS EUGENIO H.
Published: September 2013

We present an overview of the difficulties sometimes encountered when determining whether a published name following a binomen is available or infrasubspecific and unavailable, following Article 45.6 of the International Code of Zoological Nomenclature (ICZN, 1999).  We propose a dichotomous key that facilitates this determination and as a preferable method, given the convoluted and subordinate discussion, exceptions, and qualifications laid out in ICZN (1999: 49–50).  Examples and citations are provided for each case one can encounter while making this assessment of availability status of names following the binomen.
Biases in Reanalysis Snowfall Found by Comparing the JULES Land Surface Model to GlobSnow
Authors: Hancock Steven , Huntley Brian , Ellis Richard , Baxter Robert
Published: September 2013

Snow exerts a strong influence on weather and climate. Accurate representation of snow processes within models is needed to ensure accurate predictions. Snow processes are known to be a weakness of land surface models (LSMs), and studies suggest that more complex snow physics is needed to avoid early melt. In this study the European Space Agency (ESA)’s Global Snow Monitoring for Climate Research (GlobSnow) snow water equivalent and NASA’s “MOD10C1” snow cover products are used to assess the accuracy of snow processes within the Joint U.K. Land Environment Simulator (JULES). JULES is run “offline” from a general circulation model and so is driven by meteorological reanalysis datasets: “Princeton,” Water and Global Change–Global Precipitation Climatology Centre (WATCH–GPCC), and WATCH–Climatic Research Unit (CRU). This reveals that when the model achieves the correct peak accumulation, snow does not melt early. However, generally snow does melt early because peak accumulation is too low. Examination of the meteorological reanalysis data shows that not enough snow falls to achieve observed peak accumulations. Thus, the earlier studies’ conclusions may be as a result of weaknesses in the driving data, rather than in model snow processes. These reanalysis products “bias correct” precipitation using observed gauge data with an undercatch correction, overriding the benefit of any other datasets used in their creation. This paper argues that using gauge data to bias-correct reanalysis data is not appropriate for snow-affected regions during winter and can lead to confusion when evaluating model processes.
Synoptic Preconditions for Extreme Flooding during the Summer Asian Monsoon in the Mumbai Area
Authors: Lomazzi Marco , Entekhabi Dara , Pinto Joaquim G. , Roth Giorgio , Rudari Roberto
Published: September 2013

The summer monsoon season is an important hydrometeorological feature of the Indian subcontinent and it has significant socioeconomic impacts. This study is aimed at understanding the processes associated with the occurrence of catastrophic flood events. The study has two novel features that add to the existing body of knowledge about the South Asian monsoon: 1) it combines traditional hydrometeorological observations (rain gauge measurements) with unconventional data (media and state historical records of reported flooding) to produce value-added century-long time series of potential flood events and 2) it identifies the larger regional synoptic conditions leading to days with flood potential in the time series. The promise of mining unconventional data to extend hydrometeorological records is demonstrated in this study. The synoptic evolution of flooding events in the western-central coast of India and the densely populated Mumbai area are shown to correspond to active monsoon periods with embedded low pressure centers and have far-upstream influences from the western edge of the Indian Ocean basin. The coastal processes along the Arabian Peninsula where the currents interact with the continental shelf are found to be key features of extremes during the South Asian monsoon.
Scaling Turbulent Dissipation in the Transition Layer
Authors: Sun Oliver M. , Jayne Steven R. , Polzin Kurt L. , Rahter Bryan A. , St. Laurent Louis C.
Published: September 2013

Data from three midlatitude, month-long surveys are examined for evidence of enhanced vertical mixing associated with the transition layer (TL), here defined as the strongly stratified layer that exists between the well mixed layer and the thermocline below. In each survey, microstructure estimates of turbulent dissipation were collected concurrently with fine-structure stratification and shear. Survey-wide averages are formed in a “TL coordinate” zTL, which is referenced around the depth of maximum stratification for each profile. Averaged profiles show characteristic TL structures such as peaks in stratification N2 and shear variance S2, which fall off steeply above zTL = 0 and more gradually below. Turbulent dissipation rates ɛ are 5–10 times larger than those found in the upper thermocline (TC). The gradient Richardson number Ri = N2/S2 becomes unstable (Ri < 0.25) within ~10 m of the TL upper boundary, suggesting that shear instability is active in the TL for zTL > 0. Ri is stable for zTL ≤ 0. Turbulent dissipation is found to scale exponentially with depth for zTL ≤ 0, but the decay scales are different for the TL and upper TC: ɛ scales well with either N2 or S2. Owing to the strong correlation between S2 and N2, existing TC scalings of the form ɛ ~ |S|p|N|q overpredict variations in ɛ. The scale dependence of shear variance is not found to significantly affect the scalings of ɛ versus N2 and S2 for zTL ≤ 0. However, the onset of unstable Ri at the top of the TL is sensitively dependent to the resolution of the shears.
Airborne Laser Absorption Spectrometer Measurements of Atmospheric CO2 Column Mole Fractions: Source and Sink Detection and Environmental Impacts on Retrievals
Authors: Menzies Robert T. , Spiers Gary D. , Jacob Joseph
Published: September 2013

This paper provides atmospheric CO2 column abundance measurement results from a summer 2011 series of flights of a 2.05-μm laser absorption spectrometer on the NASA DC-8 research aircraft. The integrated path differential absorption (IPDA) method is used for the CO2 column mole fraction retrievals. This instrument and the data analysis methodology developed to achieve retrievals over complex terrain and variable atmospheric conditions provide insight into the capabilities of the IPDA method for both airborne measurements and future global-scale CO2 measurements from low-Earth orbit pertinent to the proposed NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission. Demonstrated in this paper is the capability to measure CO2 drawdown caused by crop activity during a midday flight over the U.S. upper Midwest area. In addition, an example is provided of high spatial resolution measurements of CO2 plumes from individual stack clusters of the Four Corners Power Plant in northwestern New Mexico. Complex terrain, the spectral properties of the aboveground scatterers, and potential cloud contamination are factors that complicate the column abundance retrieval. The impacts of these factors and various means of minimizing these influences in the retrievals are discussed.
Convection-Permitting Forecasts Initialized with Continuously Cycling Limited-Area 3DVAR, Ensemble Kalman Filter, and “Hybrid” Variational–Ensemble Data Assimilation Systems
Authors: Schwartz Craig S. , Liu Zhiquan
Published: September 2013

Analyses with 20-km horizontal grid spacing were produced from parallel continuously cycling three-dimensional variational (3DVAR), ensemble square root Kalman filter (EnSRF), and “hybrid” variational–ensemble data assimilation (DA) systems between 0000 UTC 6 May and 0000 UTC 21 June 2011 over a domain spanning the contiguous United States. Beginning 9 May, the 0000 UTC analyses initialized 36-h Weather Research and Forecasting Model (WRF) forecasts containing a large convection-permitting 4-km nest. These 4-km 3DVAR-, EnSRF-, and hybrid-initialized forecasts were compared to benchmark WRF forecasts initialized by interpolating 0000 UTC Global Forecast System (GFS) analyses onto the computational domain.

While important differences regarding mean state characteristics of the 20-km DA systems were noted, verification efforts focused on the 4-km precipitation forecasts. The 3DVAR-, hybrid-, and EnSRF-initialized 4-km precipitation forecasts performed similarly regarding general precipitation characteristics, such as timing of the diurnal cycle, and all three forecast sets had high precipitation biases at heavier rainfall rates. However, meaningful differences emerged regarding precipitation placement as quantified by the fractions skill score. For most forecast hours, the hybrid-initialized 4-km precipitation forecasts were better than the EnSRF-, 3DVAR-, and GFS-initialized forecasts, and the improvement was often statistically significant at the 95th percentile. These results demonstrate the potential of limited-area continuously cycling hybrid DA configurations and suggest additional hybrid development is warranted.
Essays on Conflicts of Interest in Medicine
Authors: Sah Sunita
Published: September 2013

The dissertation abstract and reflection commentary present the work of Dr. Sunita Sah. The abstract provides an overview of three main research questions that address conflicts of interest in medicine. Sah first explores why physicians accept gifts from pharmaceutical companies and medical device manufacturers that appear, to many critics, to be unethical. Second, she investigates situations that may increase or decrease bias in advice. Finally, Sah examines the impact of conflicted advice on advisees, particularly when they are aware of the conflict. Disclosure (informing advisees about the conflict of interest) is one of the most commonly proposed and implemented solutions to address conflicts of interest but can have surprising and unintended effects on both advisors and advisees. The reflection commentary discusses the author’s views of the research process as a junior scholar.
Retailer Corporate Social Responsibility Is Relevant to Consumer Behavior
Authors: Schramm-Klein Hanna , Zentes Joachim , Steinmann Sascha , Swoboda Bernhard , Morschett Dirk
Published: September 2013

With regard to the topicality of corporate social responsibility (CSR) in retail practice, only a few studies have comprehensively analyzed the role of CSR in retail. Due to the specific role of a retailer as a gatekeeper between the producer and the consumer in the supply chain, a comprehensive understanding of the impact of consumer perceptions of CSR activities is of great relevance. Therefore, this study contributes information regarding the impact of CSR activities on retailer performance. Using a comprehensive conceptualization of CSR, the results of our customer survey ( N = 3,313) suggest that CSR has positive implications as driver of customer loyalty and favorable consumer purchasing behavior. The authors demonstrate the CSR dimensions that are most important for retailers to influence positively consumer purchasing behavior. This study highlights the significance of the credibility of retailer CSR activities and show that consumers’ CSR orientation impacts the relationship between retailer CSR activities and consumer behavior.
That One Might Not Fall: A New Testament Theology of Food
Authors: Webster Jane S.
Published: September 2013

While we may use the Gospels and Paul’s letters to justify eating with wild abandon and enjoying every bite, we should revisit the greater principle in the New Testament: to feed others to the point of self-sacrifice in order to honor the integrity of the community.
Trial Transcript as Political Theory
Authors: Murphy Andrew R.
Published: September 2013

Political theorists can at times forget that the origins of political theory lie in the struggles of concrete political life. This paper focuses on one arena of political contestation: the collision between dissenters and their communities’ legal systems. It focuses on The Peoples Ancient and Just Liberties Asserted (1670), a purported transcript of the trial of William Penn and William Mead for disturbance of the peace. The trial plays an important role in the emergent principle of jury independence and a key role in Penn’s career as a political actor during the 1670s, culminating in his American colonizing enterprise. After a few remarks about the trial itself, the paper proceeds in two parts, each emphasizing an aspect of the text’s performative nature. First, akin to canonical works of the Anglo-American tradition, Peoples presents embedded principles: coherent and substantive visions of legitimate government, justified by reference to authoritative texts, arguments, and practices. But the defendants in Peoples also enact and embody political dissent in ways other than overt and explicit argumentation: Penn and Mead themselves appear as characters performing a politics of dissent. As a work of both political theory and political theater, Peoples offers insights into Deleuze’s notion of “dramatization,” and can lead us to a broader appreciation of the many different genres that constitute political theory.
An Investigation of Body Appreciation, Ethnic Identity, and Eating Disorder Symptoms in Black Women
Authors: Cotter Elizabeth W. , Kelly Nichole R. , Mitchell Karen S. , Mazzeo Suzanne E.
Published: September 2013

Positive body image, such as body appreciation or acceptance, has gone largely unexamined in women of color in comparison with more pathological body attitudes. In an effort to promote and extend positive body image research, this study examined the reliability and validity of the Body Appreciation Scale (BAS) in Black college women, as well as the relation between ethnic identity and body appreciation. Participants were 228 Black college women ( M age = 19.89, SD = 4.57). The relation between BAS scores and measures of appearance evaluation, self-esteem, Western beauty ideal internalization, eating disordered behavior, and teasing was examined to investigate convergent and divergent validity. Results supported the construct validity of this measure. Similar to previous research, a confirmatory factor analysis supported a unidimensional factor structure. Ethnic identity was moderately, positively associated with body appreciation. Western beauty ideal internalization mediated the relation between ethnic identity and eating, weight, and shape concerns. Overall, findings support the use of the BAS with Black college women.
A Is for Assessment
Authors: Halpern Diane F.
Published: September 2013

This is a personalized review of programs designed to assess student learning outcomes (SLOs) in higher education. In the last 30+ years, there have been few changes in the basic principles and premises. We assess SLOs for the purpose of improving teaching and learning. Although content area knowledge is important, other goals such as enhancing critical thinking skills, understanding diversity of all types, acting ethically, and communicating in appropriate ways for different audiences are equally important. Rapid increases in the use of technology have created a renewed emphasis on understanding how students learn best and thus the assessment of SLOs has moved to the center of contemporary educational debate. In addition, the goal of creating psychologically literate citizens is propelling a broad range of outcome measures.
Brief Introductory Psychology Textbooks
Authors: Griggs Richard A. , Jackson Sherri L.
Published: September 2013

It has been 12 years since the last objective analysis of brief introductory psychology textbooks was published and 13 years since the textbook copyright period used in that study, 1997–2000. Given the importance of informed textbook evaluation and selection to the introductory course but the difficulty of this task because of the large number of texts available, it is important to provide teachers with as much information as possible about introductory texts. Thus, to aid teachers in this arduous task, we objectively analyzed the most current editions of the nine brief introductory textbooks published since 2000. Our analyses also allowed us to objectively compare brief introductory texts from the 1990s with those from the 2000s.
Inhibition of the Effects of Thyroid Hormone On Rat Liver By 5,5'-Diphenylthiohydantoin
Authors: Schaffer Walter T. , Veech Richard , Mehlman Myron A. , Tobin Richard B.
Published: September 2013

Metabolites were measured in freeze-clamped livers from rats that had been maintained for 3 weeks on a stock diet supplemented with 0.1 % 5,5'-diphenylthiohydantoin (DPTH). Compared with control animals, DPTH-treated animals had lower levels of phosphoenolypyruvate and 3-phosphoglycerate and elevated ratios of [ATP]/[ADP][Pi ] and [NADP+]/[NADPH], suggesting mild hypothyroidism. Conversely, the administration of thyroxine (T4) for 5 days to animals fed the control diet resulted in elevated levels of phosphoenolpyruvate, 3-phosphoglycerate, and ketone bodies and lowered ratios of[ATP]/[ADP][Pi] and [NADP +]/[NADPH], consistent with the known effects of thyroid hormones on liver tissues. In animals simultaneously treated with DPTH and T4, the effects of thyroxine on the [NADP+]/[NADPH] ratio and the levels of phosphoenolypyruvate, 2-phosphoglycerate and ketone bodies were reversed. However, the calculated free cytoplasmic [ATP]/[ADP][Pi ] ratio and the calculated cytochrome c3+/cytochrome C2+ ratio did not return to control values. This suggests that those actions of thyroid hormone which are mediated by potentiation of adrenergic effects are reversed by DPTH. These actions include a decrease in peripheral lipolysis, a reduction of the free cytoplasmic [NADP+]/[NADPH] ratio, and an apparent inhibition of the pyruvate kinase reaction, but DPTH apparently does not reverse the effects of thyroid hormone on mitochondrial 02 consumption and A TP generation.
Pathogenesis of Phosgene Poisoning
Authors: Diller W.F.
Published: September 2013

Phosgene inhalation in concentrations > 1 ppm may produce a transient bioprotective vagus reflex with rapid shallow breathing in some individuals. Phosgene concentrations > 3 ppm are moderately irritating to eyes and upper airways. Toxic phosgene doses ( ≥ 30 ppm-min) inhaled into the terminal respiratory passages render the blood-air-barrier more permeable to blood plasma, which gradually collects in the lung. Some time passes, however, until the collection of fluid provokes signs and symptoms. This period in which the patient experiences relative well-being is known as the clinical latent phase. The clinical symptoms which follow and the pathological changes underlying them are discussed in detail; dose-effect relationships are demonstrated. The regression phase after poisoning has been overcome is briefly sketched.
Methods for Detecting Pulmonary Edema
Authors: Hedlund Laurence W. , Putman Charles E.
Published: September 2013

Pulmonary edema appears to develop in three phases: (a) after an initial injury to the lung, permeability of the air-blood barrier to water increases; (b) a subsequent increase in movement of extravascular fluid ; and (c) finally, there is a significant increase in extravascular fluid volume (interstitial and alveolar). Ideally, early detection should monitor the initial phases of pulmonary edema, namely, the injury and the increased permeability. All established clinical and most of the research methods, however, monitor only the final or volume phase of the edema process. The chest radiograph is perhaps the most commonly used method for clinical detection of pulmonary edema, although it lacks the sensitivity for assessment of edema much before clinical signs are apparent. This paper reviews some of the clinical and research methods for detecting pulmonary edema with special emphasis on radiographic methods.
Early Diagnosis of Phosgene Overexposure
Authors: Diller Werner F.
Published: September 2013

At the present time, the following parameters can be recommended for "early diagnosis" of phosgene overexposure: (a) Phosgene indicator paper badges, to be worn by all persons involved in handling phosgene (these badges permit immediate estimation of the exposure dose in each individual case); (b) Observation of the initial irritative symptoms of the eye and the upper respiratory tract after phosgene inhalation can provide a rough indication of the inhalation concentration and dose; (c) X-ray photographs of the lungs make it possible to detect incipient toxic pulmonary edema at an early stage, during the clinical latent period. A number of additional parameters require further critical investigation.
Phosgene: a Practitioner's Viewpoint
Authors: Wells B.A.
Published: September 2013

Clinical experience with five patients exposed to phosgene is described. The treatment of phosgene poisoning was focused upon the presenting problem, pulmonary edema. Arterial hypoxemia was treated with a face mask with 10 cm CPAP with the FiO2 adjusted as needed or with a volume ventilator with controlled ventilation. Ventilation was controlled to reduce the work of breathing. Metabolic acidosis was treated with NaCHO3 to produce a normal pH. A vigorous program of diuresis was used to treat the pulmonary edema. Lasix was administered to produce a negative fluid balance while maintaining a good urinary output. The negative fluid balance correlated well with reduced oxygen requirements.
A Literature Review: Therapy for Phosgene Poisoning
Authors: Diller W.F. , Zante R.
Published: September 2013

A literature search designed to collect information on therapy for phosgene poisoning has been conducted for the period 1920-1982. To achieve this goal, literature services were consulted, cross references were carefully followed and, whenever possible, unpublished reports (e.g., from Edgewood Arsenal and Porton Research Station) were evaluated. The various therapeutic agents and measures described in the literature are presented in alphabetical order. When available, detailed data are given for the phosgene dose, interval of time between exposure and institution of therapy, therapeutic effect and parameters used to assess efficacy. A final summary presents general recommendations for therapy and for further research.
Influence of Age On the Biochemical Response of Rat Lung To Ozone Exposure
Authors: Mustafa Mohammad G. , Elsayed Nabil M. , Ospital Jean J. , Hacker Allen D.
Published: September 2013

We have previously examined the influence of animal age on the pulmonary response to ozone (03) in rats between 7 and 90 days of age (Elsayed et al., 1982a). In the present study, we expanded the age groups of rats, and examined in greater detail the relationship between animal age and pulmonary response to inhaled 03. We exposed 7 groups of specific pathogen free, male Sprague-Dawley rats, aged 24, 30, 45, 60, 90, 180, and 365 days, to 0.8 ppm (1568 μg/m3) 03 continuously for 3 days. After 03 exposure, we sacrificed the exposed rats and a matched number of controls from each age group, and analyzed their lungs for a series of physical and biochemical parameters, including glutathione metabolizing and NADPH producing enzyme activities. We observed that in control rats all the parameters increased as a function of age. However, the rate of increase was generally slower after age 60 days. After 03 exposure there was an increase in all the parameters for all age groups relative to their corresponding controls, but the extent of increase was significantly larger in rats 60 days and older than in younger rats. A regression of the difference in mean values between control and exposed animals for each parameter against age showed a linear correlation, indicating that the response was agedependent. Since the magnitude of such increases is thought to reflect the degree of lung injury, the results suggest that 03 exposure causes greater lung injury in older rats than in younger rats. We tested this assumption by exposing rats from four different age groups (24, 45, 60 and 90 days) to a lethal dose of 03 (4 ppm or 7840 ug/m3 for 8 hours). The mortality rates were 50% and 83% for 24 and 45 day old rats, respectively, and 100% for 60 and 90 day old rats. The results of these studies further demonstrate that older rats are more susceptible to lung injury from 03 than younger rats.
Hydrocarbon Nephropathy in Male Rats: Identification of the Nephrotoxic Components of Unleaded Gasoline
Authors: Halder Clive A. , Holdsworth Charles E. , Cockrell Beverly Y. , Piccirillo Vincent J.
Published: September 2013

Previous subchronic and/or chronic inhalation studies of unleaded gasoline and a variety of petroleum naphthas, solvents, and distillates have shown that these complex materials are capable of inducing a distinctive nephropathy which appears limited to male rats. Therefore a series of gavage screening studies using male F-344 rats was conducted on components of gasoline to more clearly identify the major contributors to this nephrotoxicity. The dosing regimen consisted of 20 doses administered once daily, 5 days per wk for 4 wk. Tested were 15 pure hydrocarbon compounds typically found in unleaded gasoline boiling range, 4 naphtha streams representative of those commonly used to blend gasolines and 3 distillation fractions covering the less volatile portions of gasoline. The results revealed that the alkane (paraffin) components were primarily responsible for the nephrotoxic activity seen in unleaded gasoline, with a positive structure-activity response relating the degree of alkane branching to the potency of the nephrotoxic response. In addition, the nephrotoxic activity observed with the naphtha streams and distillation fraction correlated well with the proportion of branched alkanes contained in each.
Risk Assessment Extrapolations and Physiological Modeling
Authors: Clewell Harvey J. , Andersen Melvin E.
Published: September 2013

The process of assessing the risk associated with human exposure to environmental chemicals inevitably relies on a number of assumptions, estimates and rationalizations. One of the more challenging aspects of risk assessment involves the need to extrapolate beyond the range of conditions used in experimental animal studies to predict anticipated human risks. The most obvious extrapolation required is that from the tested animal species to humans; but others are also generally required, including extrapolating from high dose to low dose, from one route of exposure to another and from one exposure timeframe to another. Several avenues are available for attempting these extrapolations, ranging from the assumption of strict correspondence of dose to the use of statistical correlations. One promising alternative for conducting more scientifically sound extrapolations is that of using physiologically based pharmacokinetic models that contain sufficient biological detail to allow pharmacokinetic behavior to be predicted for widely different exposure scenarios. In recent years, successful physiological models have been developed for a variety of volatile and nonvolatile chemicals, and their ability to perform the extrapolations needed in risk assessment has been demonstrated. Techniques for determining the necessary biochemical parameters are readily available, and the computational requirements are now within the scope of even a personal computer. In addition to providing a sound framework for extrapolation, the predictive power of a physiologically based pharmacokinetic model makes it a useful tool for more reliable dose selection before beginning large-scale studies, as well as for the retrospective analysis of experimental results.
Ranking Chemicals Based On Chronic Toxicity Data
Authors: De Rosa Christopher T. , Stara Jerry F. , Durkin Patrick R.
Published: September 2013

During the past 3 years, EPA's ECA O/ Cincinnati has developed a method to rank chemicals based on chronic toxicity data. This ranking system reflects two primary attributes of every chemical: the minimum effective dose and the type of effect elicited at that dose. The purpose for developing this chronic toxicity ranking system was to provide the EPA with the technical background required to adjust the RQs of hazardous substances designated in Section 101(14) of CERCLA or "Superfund." This approach may have applications to other areas of interest to the EPA and other regulatory agencies where ranking of chemicals based on chronic toxicity is desired.
Biological Monitoring of Nickel
Authors: Sunderman F. William , Aitio Anterior , Morgan Lindsay G. , Norseth Tor
Published: September 2013

Measurements of nickel in body fluids, excreta, and tissues from humans with occupational, environmental, and iatrogenic expo sures to nickel compounds are comprehensively reviewed. Correla tions between levels of human exposures to various classes of nickel compounds via inhalation, oral, or parenteral routes and the corresponding concentrations of nickel in biological samples are critically evaluated. The major conclusions include the following points: (1) Measurements of nickel concentrations in body fluids, especially urine and serum, provide meaningful insights into the extent of nickel exposures, provided these data are interpreted with knowledge of (a) the exposure routes, sources, and durations, (b) the chemical identities and physical-chemical properties of the nickel compounds, and (c) relevant clinical and physiological information, such as renal function. (2) Nickel concentrations in body fluids should not, at present, be viewed as indicators of spe cific health risks, except in persons exposed to nickel carbonyl, for whom urine nickel concentrations provide prognostic guidance on the severity of the poisoning. (3) In persons exposed to soluble nickel compounds (e.g., NiCl2, NiSO4 ), nickel concentrations in body fluids are generally proportional to exposure levels; absence of increased values usually indicates non-significant exposure; pres ence of increased values should be a signal to reduce the exposure. (4) In persons exposed to less soluble nickel compounds (e.g., Ni3S2, NiO), increased concentrations of nickel in body fluids are indicative of significant nickel absorption and should be a signal to reduce the exposures to the lowest levels attainable with available technology; absence of increased values does not necessarily indi cate freedom from the health risks (e.g., cancers of lung and nasal cavities) associated with exposures to certain relatively insoluble nickel compounds.
Computerized Information Resources in Toxicology and Industrial Health-a Review
Authors: Halton David M.
Published: September 2013

The explosion in scientific information presents problems for toxi cologists and industrial health specialists who need to respond rapidly and comprehensively to the information needs of the pub lic, government and industry. The application of information tech nology enables large volumes of toxicology and industrial health information to be stored and retrieved through a variety of data base resources. Three different categories of databases are des cribed: dictionary, bibliographic and informational types. Examples of specific toxicology and industrial health databases within each category are given; their origin, style and content are reviewed. Specialists in the industrial health field are encouraged to improve their knowledge and literacy in the new disciplines of information technology and information science.
Increasing Trends in Some Cancers in Older Americans: Fact or Artifact?
Authors: Davis Devra Lee , Lilienfeld Abraham D. , Gittelsohn Allan , Scheckenbach Mary Ellen
Published: September 2013

In analyzing U. S. cancer mortality from 1933 to 1978, Doll and Peto speculated that recently recorded increases in mortality among those over age 64 were likely to be artifacts, reflecting deaths previously misattributed to such causes as nonspecific cancer, pneumonia, and senility and other ill-defined causes. We test this hypothesis by examining some age-specific, cause-specific mortality in persons 35 to 84 for the period of the 8-ICDA, 1968- 1978, which corresponds to the last eleven years of the period stu died by Doll and Peto. Our analysis reveals increasing trends in mortality from lung cancer, brain cancer and multiple myeloma in older whites and nonwhites along with increases in several poten tially miscoded causes of death from 1968 to 1978. Thus, these increasing cancers in the elderly cannot be explained solely as arti facts. Further studies of trends in site-specific cancer mortality should include age groups through at least age 85. Continued mon itoring of site-specific cancer mortality patterns, particularly among the elderly, remains crucial for developing preventive strategies to reduce cancers.
Behavioral Toxicity of Nitrous Oxide in Rats Following Prenatal Exposure
Authors: Mullenix Phyllis J. , Moore Paul A. , Tassinari Melissa S.
Published: September 2013

Nitrous oxide (N20) exposure has been associated with neurotoxic ity, especially peripheral neuropathy, in both humans and animals. The effects of this anesthetic gas on the central nervous system (CNS) and spontaneous behavior, however, have yet to be delin eated. Timed-pregnant Sprague-Dawley rats were exposed to 75% N2O/25% 02 on gestational days 14 and 15 or day 15 only for eight hours per day. The offspring were tested at one and five months of age; their spontaneous behavior in a novel environment was recorded in the residential maze and using time-lapse photography. The results indicated that in utero exposure to N20 permanently altered the spontaneous motor output of the CNS. This effect was most prominent in 5 month old animals, and females were affected more than males. Exposures on gestational days 14 and 15 pro duced an effect that was not only greater but also qualitatively dif ferent than that produced by exposure on day 15 only. The two- day exposure induced hyperactivity in both sexes, whereas the one- day exposure induced hyperactivity in the males and slight hypoac tivity in the females. These behavioral changes were not accompanied by physical abnormalities but nonetheless were last ing effects in need of further consideration.
The Accumulation of Pyrophosphate By Rat Hepatocytes
Authors: Gitomer William L. , Veech Richard L.
Published: September 2013

Hepatocytes that were isolated from 48 hr starved rats and incu bated in Krebs-Henseleit bicarbonate buffer containing 10 μM A23187, 10mM l-lactate, 1 mM pyruvate and 2mM l-lysine were found to contain 0.064 μmol of inorganic pyrophosphate/g wet wgt cells. Addition of either 20mM acetate or butyrate, which caused the formation of pyrophosphate in both the cytosol and the mitochondrial matrix or only the matrix, resulted in an increase of 0.915 and 1.91 μmol pyrophosphate/g wet wgt cells, respectively. The accumulation of pyrophosphate was shown to be non-linear with time and dependent on the calcium concentration of the incu bation media. In contrast, incubations containing a combination of 10 mM NH4 Cl and 5 mM ornithine, which resulted in the forma tion of pyrophosphate only in the cytosol, had a pyrophosphate content of 0.032 μmol/g wgt cells. When isolated hepatocytes that had been incubated with acetate or butyrate were subjected to dig itonin fractionation, all of the recoverable pyrophosphate was pres ent in the particulate fraction. It is concluded that pyrophosphate accumulates in isolated rat hepatocytes only in the presence of cal cium and a calcium ionophore, only within the mitochondrial matrix and only when pyrophosphate is formed within the mito chondrial matrix.
Differences in Rat Liver Enzyme-Altered Foci Produced By Chlorinated Aliphatics and Phenobarbital
Authors: Story David L. , Meierhenry Earl F. , Tyson Charles A. , Milman Harry A.
Published: September 2013

Nine chlorinated aliphatics (CAs)—1,1-dichloroethane, 1,2-dichloro ethane, 1,1,1-trichloroethane, 1,1,2-trichloroethane, trichloro ethylene, tetrachloroethylene, 1,1,1,2-tetrachloroethane, 1,1,2,2- tetrachloroethane, and hexachloroethane—were examined in a rat liver foci assay for evidence of initiating and promoting potential. Young adult male Osborne-Mendel rats (ten/group) were given partial hepa tectomies, followed 24 hr later by a single i.p. dose of either diethyl nitrosamine (30 mg/kg body weight) or CA, 1 wk later either a diet containing 0.05% (w/w) phenobarbital or daily oral gavage (5 × /wk) of CA in corn oil for 7 weeks, and sacrificed 1 wk later. Putative preneo plastic markers monitored were foci with increased γ-glutamyltrans peptidase activity [GGT( + )]. CAs were without significant effect in the initiation protocol at the maximum tolerated dose. In the promotion protocol, 1,1-dichloroethane, 1,1,2-trichloroethane, tetrachloro ethylene, 1,1,2,2-tetrachloroethane, and hexachloroethane induced significant increases in GGT( + ) foci above control levels. Two variants of GGT( + ) foci were distinguishable, one associated predominantly with phenobarbital promotion, resembling preneoplastic foci in other models, and the other associated with CA promotion, which was less intensely stained and exhibited branching, resemblingfoci undergoing redifferentiation. The marked differences in response may relate to differences in cytotoxic potential or mechanism of action of the two types of agents.
A Review of the Subchronic Toxicity of Butyl Benzyl Phthalate
Authors: Hammond Bruce G. , Levinskas George J. , Robinson Ellen C. , Johannsen Frederick R.
Published: September 2013

This review compares the subchronic toxicity of butyl benzyl phthalate (BBP) across several species. Data from the published literature as well as previously unpublished studies sponsored by Monsanto are presented. BBP-induced toxicity occurs only at relatively high levels of exposure and is dependent on the species, age and strain of test animals used. These factors should be considered in extrapolating findings from animal toxicology studies to humans when assessing the safety of BBP.
The Potential Role of Chemically Induced Hyperplasia in the Carcinogenic Activity of the Hypolipidemic Carcinogens
Authors: Butterworth Byron E. , Loury David J. , Smith-Oliver Tracey , Cattley Russell C.
Published: September 2013

Di(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizing agent resulting in substantial human exposure and environmental contamination. In a chronic bioassay, high doses of DEHP induced hepatocellular carcinomas in female Fischer-344 rats and male and female B6C3F1 mice. Thus, there is considerable concern as to the species specificity, mechanism of action, and human risk assessment of DEHP. DEHP belongs to a class of agents described as hypolipidemic hepatocarcinogens. These chemicals share the ability to induce hepatic peroxisomal proliferation and range from very weak to very potent hepatocarcinogens. Unlike most identified carcinogens, the hypolipidemic carcinogens lack DNA reactivity in sensitive cell culture systems such as the Ames test. It has been proposed that active oxygen radicals, produced as a result of peroxisomal proliferation, induce DNA damage. While this is an attractive hypothesis, no genotoxic activity has been observed in hepatocytes with peroxisomal proliferation in treated animals. Another biological activity shared by this class of compounds is their ability to stimulate liver growth or hyperplasia. This additive hyperplasia results from direct mitogenic stimulation rather than regenerative growth following liver toxicity. This hyperplasia can be dramatic, with liver to body weight ratios from treated animals reaching two to three times normal. The degree of induced hyperplasia correlates well with the carcinogenic potency of these agents, whereas genotoxicity does not correlate at all. Increased cellular growth may result in spontaneous mutational events or proniotional effects. While some feedback mechanism eventually inhibits liver growth, it is possible that key genes related to the regulation of cellular growth and cancer remain stimulated during continued administration of the chemical. Thus, determination of hyperplastic activity represents an attractive first-step approach to the short-term detection and study of the mode of action of nongenotoxic carcinogens.
Structure-Activity Relationships for Induction of Peroxisomal Enzyme Activities By Phthalate Monoesters in Primary Rat Hepatocyte Cultures
Authors: Lake Brian G. , Gray Tim J.B. , Lewis David F.V. , Beamand Jenny A. , Hodder Karen D. , Purchase Rupert , Gangolli Sharat D.
Published: September 2013

Rat hepatocytes were cultured for 70 hours with a series of four isomeric octyl and five isomeric hexyl phthalate monoesters, and their effects on peroxisomal fatly acid β-oxidation (palrnitoyl-CoA oxidation) and carnitine acetyltransferase activities determined. All nine monoesters produced dose-related increases in enzyme activities and marked quantitative compound potency differences were observed. Generally octyl isonters were more potent than hexyl isomers and 2- and 3-etlryl substituted isomers were more potent than their straight chain and 1-ethyl substituted analogs. For example, mono(2-ethylhexyl)phthalate was more potent than mono(1-ethylhexyl)phthalate, and this was also observed after oral administration of the two isomers to rats for seven days. The cell culture data for induction of palmitoyl-CoA oxidation were used to generate quantitative structure-activity relationships. Relatively poor correlations were observed between biological activity and simple hydrophobic parameters, but a good correlation was obtained when compound electronic structural parameters, obtained by molecular orbital calculations, were employed. These studies demonstrate relationships between biological activity and chemical structure for a series of phthalate monoesters and indicate the potential usefulness of primary rat hepatocyte cultures to screen compounds for peroxisome proliferation.
Metabolic and Peroxisome Proliferation Studies With Di(2-Ethylhexyl)Phthalate in Rats and Monkeys
Authors: Short Robert D. , Robinson Ellen C. , Lington Arthur W. , Chin Arthur E.
Published: September 2013

Male Fischer 344 rats and cynomolgus monkeys were treated with various doses of di(2-ethylhexyl)phthalate (DEHP) for at least 21 days. There was metabolic, biochemical, and morphological evidence for peroxisomal proliferation in rats that consumed diets containing 1000 ppm DEHP and above. These diets were estimated to provide average daily doses of about 100 mg/kg of DEHP. In contrast, peroxisomal proliferation was not observed in monkeys that received up to 500 mg/kg/day of DEHP by gavage. The results of this study suggest that rats do not provide a good model for predicting the results of DEHP exposure on peroxisomal proliferation in higher primates.
Persistence of Vanadium Compounds in Lungs after Intratracheal Instillation in Rats
Authors: Sharma Raghubir P. , Flora Swaran J.S. , Drown David B. , Oberg Steven G.
Published: September 2013

Translocation and tissue distribution of two different forms of vana dium compounds, orthovanadate (soluble) and vanadium pentox ide (less soluble), were investigated. Groups of randomly selected rats were injected intratracheally with radiolabeled vanadium (48V) compounds and the animals were sacrificed at 1, 7 and 28 days after treatment. Blood, lungs and other major organs and tissues, namely liver, kidney, spleen, heart, testes, brain, muscle, and bone were sampled and the vanadium contents determined by gamma spectrometry. The less soluble form of vanadium (vanadium pent oxide) was eliminated from the lungs at a slow but exponentially linear rate, whereas the soluble form was translocated rapidly from this organ and exhibited a non-linear decline. Compared to the less soluble form, significantly less vanadium was retained in lungs 7 and 28 days after intratracheal instillation of vanadate. One day after treatment significantly higher concentrations (approximately 4 times) of vanadium after orthovanadate were observed in liver, kidney, spleen and bone compared to the pentoxide. However, tissue residues at 7 and 28 days indicated that both forms of vanadi um were rapidly eliminated, except from bone and lungs. Results suggest a prolonged retention of less soluble forms of vanadium and possible health effects following repeated occupational expo sure.
Risk Assessment and Oncodynamics of Ethylene Oxide as Related to Occupational Exposure
Authors: Beliles Robert P. , Parker Jean C.
Published: September 2013

Two rat inhalation bioassays have been integrated into the risk assessment on the carcinogenicity of ethylene oxide (EO). The car cinogenic findings as well as relevant metabolism and pharmacoki netic data are reviewed. Brain tumors were selected as the endpoint for the assessment of risk because of the indication that adverse effects on the nervous system, related to EO exposure, were con sistent across species. Two methods, time-exposure concentration product and area under the plasma concentration-time curve (A UC) are used as a basis for calculating effective dose. Scaling of the dose to man from both rat and dog is explored based on phar macokinetic studies. Two different mathematical risk extrapolation models, the probit and the multi-stage, are used to estimate the cancer risk for daily exposures to EO of 1.8 μg/liter over a working lifetime. The use of A UC as a basis for dose from a daily exposure of 1.8 μg/liter over a working lifetime gives the higher risk rates (90-142/10,000 workers). The implication of the simulated dose using plasma concentrations versus the time-concentration product approach is discussed in relation to threshold effects.
Correspondence of Results From Hepatocyte Studies With in Vivo Response
Authors: Tyson Charles A.
Published: September 2013

Isolated hepatocyte systems are being examined in our laboratory for a number of applications, including alternatives to animal test ing. This report summarizes findings from studies with chlorinated aliphatics, acetaminophen, nitrotoluenes, and cyanide and its anti dotes that relate to in vivo toxicity and validation of these systems for cytotoxicity screening.