bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociative chemisorption of methane on Ni(100): Threshold energy from CH4(2ν3) eigenstate-resolved sticking measurements
Authors: Abbott H. L. , Bukoski A. , Kavulak D. F. , Harrison I.
Published: September 2003

A three-parameter microcanonical theory of gas-surface reactivity is used to model the dissociative sticking of vibrationally excited methane with two quanta of energy in the ν3 antisymmetric C–H stretch. An apparent threshold energy for C–H bond cleavage of CH4 incident on Ni(100) of 65 kJ/mol is found, in quantitative agreement with ab initio quantum chemistry calculations but 38 kJ/mol less than GGA-DFT calculations. Successful microcanonical analysis and prediction of recent thermal equilibrium and various nonequilibrium dissociative chemisorption experiments for methane on Ni(100) provide no evidence for mode-specific reactivity.
High-quality nonalloyed rhodium-based ohmic contacts to p-type GaN
Authors: Song June O , Leem Dong-Seok , Kwak Joon Seop , Nam O. H. , Park Y. , Seong Tae-Yeon
Published: September 2003

We report on a promising Rh-based scheme for high-quality ohmic contacts to surface-treated p-GaN:Mg (4×1017 cm−3). It is shown that the two-step surface-treated Rh contacts (10 nm) produce a specific contact resistance of 1.7×10−5 Ω cm2. It is also shown that the two-step treated Rh/Ni (5/5 nm) and Rh/Au (5/5 nm) contacts yield 6.0×10−5 and 9.3×10−6 Ω cm2, respectively. Based on the current–voltage measurement, x-ray photoemission spectroscopy, and Auger electron spectroscopy results, the mechanisms for the formation of the nonalloyed Rh-based ohmic contacts is described and discussed.
Water–silica surface interactions: A combined quantum-classical molecular dynamic study of energetics and reaction pathways
Authors: Du Mao-Hua , Kolchin Andrew , Cheng Hai-Ping
Published: September 2003

We report studies of water–silica surface interactions using a hybrid first-principles–classical molecular dynamics simulation method. The quantum region, which is treated with high accuracy density functional theory, is embedded in a large amorphous matrix described by classical potentials. With this model, both nondissociative and dissociative processes of water molecules at a two-membered ring site, which has been found experimentally on the surface, are studied. Our investigations provide qualitative and quantitative descriptions of the reaction pathways and energy landscape. A barrier-free double hydrogen atom transfer process is observed.
Blanchability of peanut (Arachis hypogaea L.) kernels: early generation selection and genotype stability over three environments
Authors: Cruickshank A. W. , Tonks J. W. , Kelly A. K.
Published: September 2003

Blanching is the removal of testa from peanut kernel by heating followed by abrasion. Blanchability is the capacity to recover kernels with all the testa removed. This study investigated the response to early generation selection for blanchability and the stability of 22 breeding lines over 3 environments.F2-derived families with 'good' and 'poor' blanchability were selected. BLUPs for F4:5 lines from F2 families were significantly correlated with the mean blanchability of F2:3 rows. The within-family variance was mostly in 3�of the poor blanching families. In all other families, variance among lines within families was smaller than the error variance. Early generation selection was effective.In the 22 lines × 3 site experiment, there was a high genetic correlation common to each pair of sites, suggesting that differences in blanchability are repeatable. The expression of genetic variation was much greater at Coominya, with a 5-fold greater genetic variance than at Walkamin. All 3 environments in this experiment were irrigated. Interaction may have been greater with the inclusion of rainfed environments.Parent selection could make an important contribution to breeding for improved blanchability. Environment may not substantially affect the rank of genotypes but may affect the capacity to detect differences.
The response to moisture and defoliation stresses, and traits for resilience of perennial grasses on the Northern Tablelands of New South Wales, Australia
Authors: Boschma S. P. , Hill M. J. , Scott J. M. , Rapp G. G.
Published: September 2003

A field experiment was conducted to study the effects of defoliation and moisture stresses on perennial pasture grasses and to identify traits associated with their resilience. The experiment, conducted near Armidale on the Northern Tablelands of NSW, studied 4 introduced perennial grass species (Phalaris aquatica, Festuca arundinacea, Dactylis glomerata, and Lolium perenne) and 2 native grass species (Microlaena stipoides and Austrodanthonia richardsonii) subjected to 3 moisture regimes (non-stress moisture, moderate drought, and severe drought) and 2 defoliation intensities (severe and moderate). Basal area, herbage mass, phenological growth stage, nitrogen concentration, root mass, and rooting depth were compared over 2 independent 6-month periods: spring–summer (1 September 1994–28 February 1995) and summer–autumn (1 December 1994–31 May 1995). Multiple regression was used to determine which traits were important for determining plant resilience.The differences between species and their respective responses were evident in the traits measured. In general, basal area tended to increase over summer and show little change during autumn. Severe defoliation stimulated plant growth, resulting in higher harvested herbage mass than from those moderately defoliated. Reproductive development was suppressed by severe drought and reduced by moderate drought. Severe defoliation suppressed flowering of Dactylis and Lolium at both drought intensities, compared with moderate defoliation. Phalaris, Festuca, and Austrodanthonia were the deepest rooting species during spring–summer, and Dactylis the shallowest. All species had similar rooting depths during summer–autumn, with those under severe and moderate drought having the deepest and shallowest rooting, respectively.Carbohydrate reserves and basal area were important traits for determining plant resilience during spring–summer. During summer–autumn, maintaining basal area and plant biomass through moderate grazing was important for resilience.
Comparing wheat grown in South Australian organic and conventional farming systems. 1. Growth and grain yield
Authors: Kitchen J. L. , McDonald G. K. , Shepherd K. W. , Lorimer M. F. , Graham R. D.
Published: September 2003

Organic farming standards do not allow addition of water-soluble fertilisers and therefore it is likely that growth of organically grown crops will be limited by nutrient availability. However, in marginal rainfall conditions, when growth in conventional systems is limited by water availability, yields of organically grown crops could be comparable with those conventionally grown. Similarly, micronutrient-efficient plant varieties could be expected to perform comparatively better under organic farming conditions than they do in conventional systems, when compared with micronutrient-inefficient varieties.In this study, biomass and grain production of wheat from certified organic farming systems were compared with neighbouring conventional farming systems in 'across the fence' field trials in 1 moderate and 2 marginal rainfall areas of South Australia. Wheat varieties compared included 2 old wheat varieties developed under relatively low-input conditions (Baroota Wonder and Dirk-48) and varieties shown to be micronutrient-efficient (Janz and Trident) and inefficient (Yallaroi).The organic farming systems produced significantly less biomass than the conventional farming systems at late tillering in both the moderate and marginal rainfall areas. Grain yield was variable, but significantly lower in the organic farming system for 11 of the 14 comparisons. None of the varieties showed an adaptive advantage for 1 farming system over the other. The relative yield of the organic system, compared with the conventional system, was not associated with rainfall.
Chemical manipulation of Leptosphaeria maculans (blackleg disease) pseudothecial development and timing of ascospore discharge from canola (Brassica napus) residues
Authors: Wherrett A. D. , Sivasithamparam K. , Barbetti M. J.
Published: September 2003

A study was carried out to establish key developmental stages of Leptosphaeria maculans on canola residues leading up to ascospore discharge and how these stages could be affected by chemicals. The residues were dipped in a range of chemicals, including fungicides, herbicides, and surfactants, to determine possible manipulative effects of the chemicals on the development of the fungus including ascospore discharge. Treated residues were placed in the field during the growing season. Ascospore discharge was found to be closely related to pseudothecial maturity and density. There was no significant difference between pseudothecial maturation on the crown component compared with the stem component. A high correlation between rainfall and pseudothecial density suggested that rainfall was a good complimentary indicator for timing of ascospore discharge. These results may provide the canola industry with a potential method of monitoring pseudothecial development for estimating disease hazards. This would allow manipulation of sowing times so as to minimise or avoid heavy ascospore showers coinciding with the early seedling phase. Twenty chemical treatments showed significant efficacy in decreasing ascospore numbers early in the season, most often by delaying the development of the pseudothecia on the residues. Two scenarios were formulated giving growers the potential to manipulate pseudothecial development and/or ascospore discharge. Firstly, a number of chemicals, such as fluquinconazole, technical grade flutriafol, and gluphosinate-ammonium, were able to delay pseudothecial development and subsequent ascospore discharge was decreased by 100%, 99%, and 96%, respectively. This scenario gives growers the potential to minimise synchronisation of ascospore discharge with early crop establishment. Secondly, a situation where pseudothecial development is not delayed, but number of ascospores discharged is reduced (e.g. ziram by 45%) would only be effective if the reduction resulted in a less severe disease epidemic. There is significant potential for development of commercial chemical treatments of residues to reduce disease pressure on seedlings.
Replacement of limestone with calcite prill derived from underground water in diets for molted layer hens
Authors: Pluske J. R. , Anderson R. D.
Published: September 2003

Two hundred and forty, approximately 100-week-old molted Hyline Grey layer birds were used to compare the efficacy of calcite (CaCO3) prill (derived from an underground water lime treatment process for the removal of hardness; hereafter referred to as 'calcite prill') or limestone ('control') added as supplementary sources of calcium (Ca) to layer diets. One hundred and twenty birds were allocated to each diet. The 120 birds derived from 8 pens, with each pen comprising 5 cages each of 3 birds (15 birds per pen). The 2 diets were formulated to provide equal amounts of nutrients and vitamins and minerals, with the calcite prill and limestone added to each diet at 70�g/kg. Diets were offered on an ad libitum basis for 5 weeks. Measurements of bird performance, egg production, and egg quality were determined on a weekly basis. There were no statistical differences (P > 0.05) between the 2 diets in any of the indices measured over the experimental period. The average hen day percent was 73.2% and 69.5% for calcite-prill-fed birds and control birds, respectively. The lack of differences in egg production, egg weights, and egg quality seen between birds fed calcite prill and those fed limestone suggests that the Ca in calcite prill has a bioavailability at least equal to that for Ca from limestone. In this regard, calcite prill would appear to be a suitable alternative to limestone in diets for layer birds of this age.
Yield limiting potential of necrotic and non-necrotic strains of Bean yellow mosaic virus in narrow-leafed lupin (Lupinus angustifolius)
Authors: Jones R. A. C. , Coutts B. A. , Cheng Y.
Published: September 2003

The yield losses caused by necrotic and non-necrotic strains of Bean yellow mosaic virus (BYMV) in narrow-leafed lupin (Lupinus angustifolius) were quantified in field experiments. Clover plants infected with either were introduced into plots to provide infection sources, and aphids spread infection to the lupin plants. When the effects of virus infection were examined in individual lupin plants infected with necrotic BYMV, they were killed by early infection so there was no seed production. With late infection, shoot dry wt, seed yield, and seed number were decreased by at least 55%, 80%, and 74%, respectively. With non-necrotic BYMV, shoot dry wt, seed yield, and seed number diminished with increasing duration of plant infection, these decreases ranging over 27–88%, 48–99%, and 35–98% for late to early infection, respectively. In partially infected stands in which both necrotic and non-necrotic BYMV were spreading, an additional incidence of 28% in plots with introduced non-necrotic strain foci over that in plots without introduced foci was sufficient to decrease overall seed yield significantly. However, an additional incidence of 10% was insufficient to do so in plots with introduced necrotic strain foci. In plots into which different numbers of clover plants infected with non-necrotic BYMV were introduced, subsequent incidence of infection depended on the magnitude of the initial virus source, and yield was decreased by 21–24%, 31–43%, and 64–66% with 4, 8, or 16 foci/plot, respectively. With both types of strain, yield loss in infected plants was mainly due to failure to produce any seed or to fewer seeds being produced, but smaller seed size also contributed. These results show that non-necrotic strains of BYMV have considerable yield-limiting potential in narrow-leafed lupin crops despite causing milder symptoms than necrotic strains. No evidence was obtained of seed-transmission of non-necrotic BYMV in narrow-leafed lupin, but a 0.2% seed transmission rate was detected in yellow lupin (Lupinus luteus).
A Large Scale Application of Slon Magnetic Separator in Meishan Iron Ore Mine
Authors: Dahe Xiong
Published: September 2003

Meishan Iron Mine processes 4 million tons of iron ore and produces about 2.6 million
tons of iron concentrate annually. Because of a relatively high content of phosphorus,
the iron concentrate does not meet the market requirements. In recent years, 18 SLon‐
1500 magnetic separators have been applied to reduce phosphorus to upgrade the
concentrate quality. This paper describes research, test work and industrial application
of SLon magnetic separator in the mine.
The Sensitizer 2,4-Dinitrofluorobenzene Activates Caspase-3 and Induces Cell Death in a Skin Dendritic Cell Line
Authors: Cruz Maria Teresa , Duarte Carlos B. , Gonçalo Margarida , Figueiredo Américo , Carvalho Arsélio P. , Lopes Maria Celeste
Published: September 2003

In this work, a dendritic cell line derived from mouse skin (FSDC) was used, as an in vitro experimental model, to evaluate the cytotoxic effect of two chemical sensitizers, a strong sensitizer (2,4-dinitrofluorobenzene, DNFB) and a weak sensitizer (2,4-dichloronitrobenzene, DCNB). The results indicated that DNFB reduces the cellular metabolism of FSDC, as evaluated by the reduction of the tetrazolium salt, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). All the DNFB concentrations tested, ranging from 5.2 μ M to 26 μM, significantly inhibited the MTT reduction after 1 hour of cell exposure to the sensitizer. In contrast, incubation of FSDC with the weak sensitizer DCNB had no significant effect on the MTT reduction assay. When the cells were incubated with DNFB (13 μ M), for 3 and 6 hours, morphological changes characteristics of cell death by apoptosis were observed, as assessed by propidium iodide (PI) DNA staining and annexin-V externalization analysis. These results correlate well with an increase of caspase-3-like activity after FSDC exposure to DNFB (13 μM) for 6 hours. Together, these results indicate that apoptotic death of skin dendritic cells occurs after exposure to the sensitizer DNFB, although necrotic cell death was also observed when the cells were incubated with high concentrations of DNFB (26 μM), or after long periods of cell exposure to the chemical DNFB (13 μM, for 6 hours).
Cis-Urocanic Acid Increases Immunotoxicity and Lethality of Dermally Administered Permethrin in C57BL/6N Mice
Authors: Prater M. R. , Gogal R. M. , Blaylock B. L. , Holladay S. D.
Published: September 2003

Immunomodulatory effects of a single topical permethrin exposure, 5-day exposure to cis-urocanic acid (c UCA), or a combination of the two chemicals were evaluated in 4- to 5-week-old female C57BL/6N mice. Permethrin alone decreased thymic weight and cellularity. Although c UCA alone did not affect thymic end points, coexposure to topical permethrin and c UCA exacerbated the thymolytic effects of permethrin. The single topical dose of permethrin also depressed several immune responses in isolated splenic leukocytes. This included splenic T-cell proliferative response to mitogen, splenic macrophage hydrogen peroxide production, and splenic B lymphocyte-specific antibody production. Unlike the effect of coexposure to these agents on thymic end points, c UCA did not exacerbate permethrin's adverse effect on any of the splenic end points examined. These results appear to suggest divergent mechanisms by which these compounds affect precursor and functionally mature T cells. At the doses used in this study, permethrin caused neurotoxic effects, including lethality, in a portion of the mice. For undetermined reasons, c UCA significantly increased the rate of lethality caused by permethrin. Although the permethrin doses used in this study exceed that typically used in human medicine, these results raise some concerns about the possibility that sunlight, via c UCA, may increase the risk of adverse central nervous system and immune effects caused by permethrin alone.
Extent and Timeliness of Tissue Repair Determines the Dose-Related Hepatotoxicity of Chloroform
Authors: Anand Sathanandam S. , Soni Madhusudan G. , Vaidya Vishal S. , Murthy Subramanyam N. , Mumtaz Moiz M. , Mehendale Harihara M.
Published: September 2003

As a part of mixture toxicity studies, the objective of the present investigation was to validate the hypothesis that the rate and extent of liver tissue repair response to a given dose determines the end result of toxicity (death or recovery), regardless of the mechanisms by which injury is inflicted, using a well-known environmental pollutant, chloroform (CHCl3). In future, the data will be used to compare with the results of mixtures containing CHCl3 to aid in characterizing the safety of chemical mixtures and to construct a physiologically based pharmacokinetic (PBPK) model for dose, route, and species extrapolation. Hepatotoxicity and tissue repair were measured in male Sprague-Dawley rats (S–D) receiving a 10-fold dose range of CHCl3 (74, 185, 370, and 740 mg/kg, IP) during a time course of 0 to 96 hours. Liver injury, as assessed by plasma alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) elevation, increased with dose over the 10-fold dose range. Because CHCl3 is also known to cause kidney damage, blood urea nitrogen (BUN) and creatinine were measured to evaluate the kidney injury. With doses up to 370 mg/kg, liver injury increased in a dose-related fashion, which peaked at 24 hours and returned to normal after 48 hours, whereas at highest dose (740 mg/kg), the injury was progressive resulting in 90% mortality. Blood and liver CHCl3 levels were quantified using gas chromatography (GC) over a time course of 30 to 360 minutes. The dose-related increase in the blood and liver CHCl3 levels were consistent with dose-dependent liver injury. Tissue regeneration response, as measured by [3H]-thymidine incorporation into hepatocellular nuclear DNA peaked at 36 hours in rats treated with the lower two doses of CHCl3 (74 and 185 mg/kg). Further increase in CHCl3 dose to 370 mg/kg resulted in an earlier increase in [3H]-thymidine incorporation at 24 hours, which peaked at 36 hours. However, at the highest dose of CHCl3 (740 mg/kg), tissue repair was delayed and attenuated, allowing for unrestrained progression of liver injury. The kidney injury markers after CHCl3 administration were not different from controls. These results support the concept that in addition to the magnitude of tissue repair response, the time at which this response occurs is critical in restraining the progression of injury. Measuring tissue repair and injury as simultaneous biological responses to toxic agents might increase the usefulness of dose-response paradigms in predictive toxicology and risk assessment. Although the dosimetry of the present study was well beyond the environmental exposure levels of CHCl3, a PBPK model will be developed in future based upon these data to evaluate the effects at environmental levels.
Neurotoxicity and Immunotoxicity Assessment in CBA/J Mice with Chronic Toxoplasma gondii Infection and Single-Dose Exposure to Methylmercury
Authors: King Marquea D. , Lindsay David S. , Holladay Steven , Ehrich Marion
Published: September 2003

Toxoplasma gondii is a protozoan parasite that localizes in the brain where it can cause life-threatening disease. Methylmercury (Me Hg) is a well-documented neurotoxicant that accumulates in the brain. We investigated end points associated with immunotoxicity and neurotoxicity in mice exposed to Me Hg during a chronic T. gondii infection. Two groups of 6-week-old, female CBA/J mice were either fed 25 T. gondii tissue cysts of the ME-49 strain or given vehicle. Six weeks later, half of the mice in each group were orally gavaged with a single dose of 20 mg/kg body weight of Me Hg, creating four groups of mice (vehicle control, T. gondii, Me Hg, and T. gondii/Me Hg). Mice were sacrificed 7 days post Me Hg exposure. Me Hg exposure caused a significant decrease in mouse body weight. Me Hg administration resulted in an increase of splenic cellularity and spleen-to-body weight ratios. Me Hg had no significant effect on the percentages of CD4+, CD8+, or non-T-cell subpopulations in the spleen. Me Hg dosed mice demonstrated an increase in absolute numbers of splenic CD4+, CD8+, or non-T cells when compared to mice in control and T. gondii-infected groups. Thymic CD4+CD8+ T-cell subpopulations were decreased ( p <.05) by Me Hg with or without a concurrent T. gondii infection. There was a significant ( p <.05) increase in brain tissue cyst counts within the group exposed to both Me Hg and T. gondii (16 4, mean SE, n = 7) versus T. gondii alone (4 1, n = 8). Histopathological examination demonstrated encephalitis, gliosis, and meningitis in brains from mice infected with T. gondii. These data indicate that exposure to both Me Hg and T. gondii has synergistic effects, with effects of Me Hg especially on the immune system.
Distinguished Service Award: Evolution of Toxicology for Risk Assessment
Authors: Henry Carol J.
Published: September 2003

The science of toxicology has served society well in protecting public health and the environment. Governments, the industrial sector, and the public have relied on toxicology as the foundation to assess risks to both human and ecological populations from environmental factors, including chemicals, biologic agents, physical agents, and other stressors. To maintain its prominence, the science and practice of toxicology will need to embrace the revolution underway in biology. Systems biology and biotechnologies derived from sequencing of the human genome, referred to as “genomics,” have created exciting possibilities for application to human health and environmental risk assessment. Yet this rapid advance of science and technology can be overshadowed by inconsistency in study design and sampling strategies; by the lack of quantitative or qualitative correlations of exposure, dose, or adverse effects; and by the lack of bioinformatics tools and analytical methods necessary to manage the volume of research findings. These limitations may render results uninterpretable and difficult, if not impossible, to use in risk assessment. Recommendations will be discussed to improve integrating systems biology and genomics into risk assessment so that the inherent promise of these new approaches can be realized.
Short-Term Repeated-Dose Toxicity Profile of Archaeosomes Administered to Mice via Intravenous and Oral Routes
Authors: Omri Abdelwahab , Agnew Brian J. , Patel Girishchandra B.
Published: September 2003

Archaeosomes, liposomes made from polar ether lipids of archaea, show promise for vaccine and drug delivery applications. The potential toxicity of intravenously (14,70, or 140 mg/kg/day for 5 consecutive days) and orally (gavaged at 55,275, or 550 mg/kg/day for 10 consecutive days) administered unilamellar archaeosomes, prepared from the total polar lipids (TPLs) extracted from several species of archaea, was assessed in female BALB/c mice. Liposomes prepared from an ester phospholipid composition were included for comparative purposes. Control groups of mice were administered 0.1 ml phosphate-buffered saline (PBS) by either route. Animals were monitored at least once daily for temperature, body weight, and clinical signs of adverse reactions. One day after the last dose, the mice were sacrificed. Blood was collected for selected biochemical/enzyme analyses, and the major organs (heart, lungs, liver, spleen, kidneys) were weighed and examined macroscopically. In addition, the spleens were examined histologically. At the two lower dosages of intravenously administered vesicles, there were no significant indications of toxicity, as compared with the PBS-administered control group. At the highest intravenous dose of 140 mg/kg/day, archaeosomes prepared from the TPL of the extreme halophiles, Halobacterium salinarum and Natronobacterium magadii, indicated potential toxicity, as evidenced by clinical signs (hyperactivity and/or piloerection), drop in body temperature, and loss in body weight. Spleens from mice administered some archaeosomes types, primarily at the highest intravenous dose tested, were enlarged, had increased organ weight, and microscopic examination revealed mild to moderate expansion of the red pulp with increased numbers of hematopoietic cells, but no changes in the white pulp. There were similar clinical signs at one or more of the higher oral doses of the ester liposomes and some of the archaeosome types; however, no other apparent toxicity was observed. Based on this limited mouse study. archaeosomes were generally well tolerated after intravenous or oral delivery at the dosages so indicated in this study.
A Standardized Approach for Iris Color Determination
Authors: Niggemann Birgit , Weinbauer Gerhard , Vogel Friedhelm , Korte Rainhart
Published: September 2003

Latanoprost, the phenyl-substituted prostaglandin F2α, has been found to be an effective agent for glaucoma therapy. This prostaglandin derivative exerts ocular hypotensive activity but is also associated with an untoward side effect, namely iris color changes. Latanoprost provoked iris color changes in cynomolgus monkeys and in multicenter clinical trials. Until now photographs were taken and compared with color plates to document these changes. The disadvantage of this method is obvious, i.e., the color luminance varies between measurements due to changes in the developer. Furthermore, subjective comparison of color changes relative to color plates rendered judgment subject to impression and opinion rather than to objective data. Therefore, a computerized method using a 3-CCD video camera attached to a slit lamp was developed. The signals were transferred to a computer and a single frame, which was “frozen” by means of a “grabber card.” Camera and the computer had previously been calibrated and color plates were measured to check the standard conditions. They were evaluated by a software program displaying average color (as red, green, and blue values) of the selected area. This method provides a fast and accurate way to quantify color changes in the iris of both experimental animals and clinical trials.
Widespread Arsenic Contamination of Soils in Residential Areas and Public Spaces: An Emerging Regulatory or Medical Crisis?
Authors: Belluck D. A. , Benjamin S. L. , Baveye P. , Sampson J. , Johnson B.
Published: September 2003

A critical review finds government agencies allow, permit, license, or ignore arsenic releases to surface soils. Release rates are controlled or evaluated using risk-based soil contaminant numerical limits employing standardized risk algorithms, chemicalspecific and default input values. United States arsenic residential soil limits, 0.4–40 ppm, generally correspond to a one-in-one-million to a one-in-ten-thousand incremental cancer risk range viaingestion of or direct contact with contaminated residential soils. Background arsenic surface soil levels often exceed applicable limits. Arsenic releases to surface soils (via, e.g., air emissions, waste recycling, soil amendments, direct pesticide application, and chromated copper arsenic (CCA)-treated wood) can result in greatly elevated arsenic levels, sometimes one to two orders of magnitude greater than applicable numerical limits. CCA-treated wood, a heavily used infrastructure material at residences and public spaces, can release sufficient arsenic to result in surface soil concentrations that exceed numerical limits by one or two orders of magnitude. Although significant exceedence of arsenic surface soil numerical limits would normally result in regulatory actions at industrial or hazardous waste sites, no such pattern is seen at residential and public spaces. Given the current risk assessment paradigm, measured or expected elevated surface soil arsenic levels at residential and public spaces suggest that a regulatory health crisis of sizeable magnitude is imminent. In contrast, available literature and a survey of government agencies conducted for this paper finds no verified cases of human morbidity or mortality resulting from exposure to elevated levels of arsenic in surface soils. This concomitance of an emerging regulatory health crisis in the absence of a medical crisis is arguably partly attributable to inadequate government and private party attention to the issue.
Changes in Cross-Fostered Sprague-Dawley Rat Litters Exposed to Perchlorate
Authors: Mahle Deirdre A. , Yu Kyung O. , Narayanan Latha , Mattie David R. , Fisher Jeffrey W.
Published: September 2003

Ammonium perchlorate is used as an oxidizer in rocket fuel. It has become a groundwater contaminant, dissociating to ammonium cation and perchlorate anion. The perchlorate ion competes with iodide for uptake into the thyroid, reducing thyroid hormone production. Pregnant Sprague-Dawley rats were given either untreated or perchlorate (1 mg/kg-day) treated drinking water beginning on gestation day 2. One set of control and exposed dams was sacrificed on gestation day 20. The litters from the second set of control and exposed dams were crossed immediately after parturition and were sacrificed at postnatal day 10. Dam serum and thyroid, pooled fetal sera, and male and female pup sera were collected and analyzed for perchlorate, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). Control pups receiving perchlorate through lactation had serum levels at postnatal day 10 of 0.54 μg/ml and 0.56 μg/ml for male and female pups, respectively, whereas exposed fetuses had serum perchlorate levels of 0.38 ± 0.04 μg/ml. Female pups receiving perchlorate lactationally had significantly lower levels of serum T4 than control pups and prenatally exposed pups. Serum T4 levels in male pups were not affected by perchlorate. Serum thyroid hormone levels from gestational perchlorate exposure were restored to control values by postnatal day 10. In utero perchlorate-exposure decreased serum T4 levels in the fetus. Gestational studies in conjunction with a crossfostering study design helped discern thyroid hormonal changes caused by perchlorate exposure during the perinatal period.
Antimicrobials: Modes of Action and Mechanisms of Resistance
Authors: Mc Dermott Patrick F. , Walker Robert D. , White David G.
Published: September 2003

After six decades of widespread antibiotic use, bacterial pathogens of human and animal origin are becoming increasingly resistant to many antimicrobial agents. Antimicrobial resistance develops through a limited number of mechanisms: (a) permeability changes in the bacterial cell wall/membrane, which restrict antimicrobial access to target sites; (b) active efflux of the antimicrobial from the cell; (c) mutation in the target site; (d) enzymatic modification or degradation of the antimicrobial; and (e) acquisition of alternative metabolic pathways to those inhibited by the drug. Numerous bacterial antimicrobial resistance phenotypes result from the acquisition of external genes that may provide resistance to an entire class of antimicrobials. These genes are frequently associated with large transferable extrachromosomal DNA elements called plasmids, on which may be other mobile DNA elements such as transposons and integrons. An array of different resistance genes may accumulate on a single mobile element, presenting a situation in which multiple antibiotic resistance can be acquired via a single genetic event. The versatility of bacterial populations in adapting to toxic environments, along with their facility in exchanging DNA, signifies that antibiotic resistance is an inevitable biological phenomenon that will likely continue to be a chronic medical problem. Successful management of current antimicrobials, and the continued development of new ones, is vital to protecting human and animal health against bacterial pathogens.
Fire Ant Venom Alkaloid, Isosolenopsin A, a Potent and Selective Inhibitor of Neuronal Nitric Oxide Synthase
Authors: Yi G. B. , Mc Clendon D. , Desaiah D. , Goddard J. , Lister A. , Moffitt J. , Vander Meer R. K. , de Shazo R. , Lee K. S. , Rockhold R. W.
Published: September 2003

Massive, multiple fire ant, Solenopsis invicta, stings are often treated aggressively, particularly in the elderly, despite limited evidence of systemic toxicity due to the venom. Over 95% of the S. invicta venom is composed of piperidine alkaloid components, whose toxicity, if any, is unknown. To assess a possible pharmacological basis for systemic toxicity, an alkaloid-rich, protein-free methanol extract of the venom from whole ants was assayed for inhibitory activity on the following nitric oxide synthase (NOS) isoforms, rat cerebellar neuronal (n NOS), bovine recombinant endothelial (e NOS), and murine recombinant immunologic (i NOS). Cytosolic NOS activity was determined by measuring the conversion of [3H]arginine to [3H]citrulline in vitro. Rat n NOS activity was inhibited significantly and in a concentration-dependent manner by the alkaloid-rich venom extract. For n NOS, enzyme activity was inhibited by approximately 50% with 0.33 ± 0.06 μgg of this venom extract, and over 95% inhibition of the three isoforms, n NOS, e NOS, and i NOS, was found with doses of 60 μg in 60-μl reaction mixture. These results indicate that the alkaloid components of S. invicta venom can produce potent inhibition of all three major NOS isoforms. Isosolenopsin A ( cis-2-methyl-6-undecylpiperidine), a naturally occurring fire ant piperidine alkaloid, was synthesized and tested for inhibitory activity against the three NOS isoforms. Enzyme activities for n NOS and e NOS were over 95% inhibited with 1000 μM of isosolenopsin A, whereas the activity of i NOS was inhibited by only about 20% at the same concentration. The IC50 for each of three NOS isoforms was approximately 18 ± 3.9 μM for n NOS, 156 ± 10 μM for e NOS, and >1000 μM for i NOS, respectively. Kinetic studies showed isosolenopsin A inhibition to be noncompetitive with L-arginine ( Ki = 19 ± 2 μM). The potency of isosolenopsin A as an inhibitor of n NOS compares favorably with the inhibitory potency of widely used n NOS inhibitors. Inhibition of NOS isoforms by isosolenopsin A and structurally similar compounds may have toxicological significance with respect to adverse reactions to fire ant stings.
Animal Drug Human Food Safety Toxicology and Antimicrobial Resistance—The Square Peg
Authors: Greenlees Kevin J.
Published: September 2003

This paper presents the traditional approach for the evaluation of human food safety used for animal drugs intended for food animals, and describes some of the difficulties posed by antimicrobial drug resistance. Like human drugs, animal drugs must be safe and effective for the patient. However, unlike human drugs, food derived from animals treated with the animal drug must also be shown to be safe for human consumption. The Food and Drug Administration has come to realize that antimicrobial drugs used in the treatment of the food animal have the potential to create a unique residue—increased numbers of microorganism that are resistant to antimicrobial drug treatment. The traditional toxicological paradigm for chemical residues does not apply to this unique microbiological residue. Information useful to a food safety evaluation may include the potential for the animal antimicrobial drug to diminish the susceptibility of microorganisms to human antimicrobial drugs, any human medical use of the drug, relationship to other human antimicrobial drugs, and the ability of the animal drug to alter the susceptibility of relevant microorganism to important human antimicrobial drugs. Yet to be developed are standardized approaches to quantify an acceptable level of resistant microorganism in food and to mitigate the hazard to assure that there is a reasonable certainty of no harm following the consumption of the edible food derived from the treated animal.
Comparison of In Vivo (Draize Method) and In Vitro (Corrositex Assay) Dermal Corrosion Values for Selected Industrial Chemicals
Authors: Stobbe Jody L. , Drake Kevin D. , Maier Kurt J.
Published: September 2003

Skin irritation is a common occupational hazard for employees engaged in the manufacture, transport, and use of industrial chemicals. The most common method used to evaluate dermal irritation and/or corrosion has typically been in vivo tests using rabbits (Draize method). Several in vitro test methods have been developed, with Corrositex being the first to gain approval by a regulatory agency (U.S. Department of Transportation). The purpose of this study was to compare the results of in vitro (Corrositex) assays of dermal irritation/corrosion to in vivo test data for several industrial chemical formulations and to determine the predictability and usefulness of the Corrositex assay for these types of products. Twenty-four (24) formulations were qualified, categorized, and evaluated using the Corrositex method and the results compared to available animal data for each of the formulations. The Corrositex assay accurately predicted a corrosive end point in 8 (57.1%) of the 14 formulations identified as corrosive by the in vivo evaluations. Corrositex accurately predicted a noncorrosive end point for 1 (10%) of 10 formulations determined to be noncorrosive in animal studies. The Corrositex assay overpredicted the packing group for 12 (50%) of the 24 formulations, and underpredicted the packing group for 7 (29.2%) of the 24 formulations. Compared to the in vivo results, Corrositex correctly classified as corrosive or noncorrosive 37.5% of the formulations tested. A concordance of 20.8% for the packing group assignments of the evaluated formulations was calculated. The Corrositex assay did not accurately predict a corrosive end point or packing group assignment for all of the formulations used in this study. Manufacturers should assess the relevance of this method to their products prior to relying on it for compliance with hazardous material and worker safety regulations.
Effects of Brevetoxins on Murine Myeloma SP2/O Cells: Aberrant Cellular Division
Authors: Han Thomas K. , Derby Melissa , Martin Dean F. , Wright Scott D. , Dao My Lien
Published: September 2003

Massive deaths of manatees ( Trichechus manatus latirostris) during the red tide seasons have been attributed to brevetoxins produced by the dinoflagellate Karenia brevis (formerly Ptychodiscus breve and Gymnodinium breve). Although these toxins have been found in macrophages and lymphocytes in the lung, liver, and secondary lymphoid tissues of these animals, the molecular mechanisms of brevetoxicosis have not yet been identified. To investigate the effects of brevetoxins on immune cells, a murine myeloma cell line (SP2/O) was used as a model for in vitro studies. By adding brevetoxins to cultures of the SP2/O cells at concentrations ranging from 20 to 600 ng/ml, an apparent increase in proliferation was observed at around 2 hours post challenge as compared to the unchallenged cell cultures. This was followed by a drop in cell number at around 3 hours, suggesting an aberrant effect of brevetoxins on cellular division, the cells generated at 2 hours being apparently short-lived. In situ immunochemical staining of the SP2/O cells at 1 and 2 hour post challenge showed an accumulation of the toxins in the nucleus. A 21-k Da protein was subsequently isolated from the SP2/O cells as having brevetoxin-binding properties, and immunologically identified as p21, a nuclear factor known to down-regulate cellular proliferation through inhibition of cyclindependent kinases. These data are the first on a possible effect of brevetoxins on the cell cycle via binding to p21, a phenomenon that needs to be further investigated and validated in normal immune cells.
Effects of Lead on Na+-K+ ATPase and Ca+2 ATPase Activities and Lipid Peroxidation in Blood of Workers
Authors: Yücebilgiç Güzide , Bilgin Ramazan , Tamer Lülüfer , Tükel Seyhan
Published: September 2003

Lead is considered one of the major environmental toxicants that causes hematological, neurological, and gastrointestinal dysfunction. In this study, the authors examined the relationship between lead and lipid peroxidation, lead and Na+-K+ ATPase activity, and lead and Ca+2 ATPase activity in blood of workers. The working group consisted of 30 male workers occupationally exposed to lead at least for 10 years. The control group consisted of 20 healthy male individuals not involved with job-related lead exposures. Blood lead content of the control group and the working group were 10.0 ± 1.8 γg/dl and 317.3 ± 47.6 γg/dl, respectively. Malondialdehyde (MDA) value of the working group (0.57 ± 0.30 nmol MDA/ml) was significantly greater than MDA value of the control goup (0.17 ± 0.02 nmol MDA/ml). In the working group, both Na+-K+ ATPase activity (105.0 ± 47.0 nmol Pi mg protein-1 h-1) and Ca+2 ATPase activity (58.0 ± 40.0 nmol Pi mg protein-1 h-1) were lower compared with the corresponding values of Na+-K+ ATPase activity (247.0 ± 41.0 nmol Pi mg protein-1 h-1) and Ca+2 ATPase activity (230.0 ± 41.0 nmol Pi mg protein-1 h-1) of normal controls. The results show that lead exposure causes inhibition of Na+-K+ ATPase and Ca+2 ATPase activities and also results in increased lipid peroxidation.
Antibiotic Resistance: Who Is Winning the War? Introductory Remarks
Authors: Sheldon Albert T.
Published: September 2003

The evolutionary response of bacteria, fungi, viruses, and parasites to the selective pressure exerted by antimicrobial agents is the emergence of populations that resist the action of the antimicrobial. The emergence and dissemination of such resistance in a variety of these pathogens is a growing public health concern. In response, the scientific community developed an action plan to address this public health issue. Antimicrobial, antifungal, and antiviral drug development for the treatment of diseases caused by resistant pathogens is one component of this strategy. In addition, due to the targeting of specific drugs against resistant pathogens, we may more readily accept a given drugs toxicity profile for the added therapeutic benefit. This symposium provides a discussion of the modes of action and mechanisms of resistance to antimicrobial agents, and the use of surveillance systems to help understand the nature and magnitude of resistance. The goal is to help guide antimicrobial drug product development and use. Specific toxicity issues are presented that should be considered in phase 1 development of antimicrobial drug products for use in clinical medicine and veterinary medicine. Finally, the national and global strategies developed by federal agencies in the Public Health Action Plan to Combat Antimicrobial Resistance are outlined.
Evaluation of Reproductive Development Following Intravenous and Oral Exposure to DEHP in Male Neonatal Rats
Authors: Cammack Jon N. , White Randy D. , Gordon Donovan , Gass Jerome , Hecker Lawrence , Conine David , Bruen Uma Swamy , Friedman Mitchell , Echols Charles , Yeh Tony Y. , Wilson Daniel M.
Published: September 2003

Di-(2-ethylhexyl)phthalate (DEHP) was administered to 3- to 5-day-old male Sprague-Dawley rats by daily intravenous injections of 60, 300, or 600 mg/kg/day or by daily oral gavage of 300 or 600 mg/kg/day for 21 days. Histopathological evaluation and organ weight measurements were performed on some animals after 21 days of dosing (primary group) and later on the recovery group animals that were held without further treatment until sexual maturity at approximately 90 days of age. No effects of any type were observed in animals treated intravenously with 60 mg/kg/day. Testicular changes, consisting of a partial depletion of the germinal epithelium and/or decrease in diameter of seminiferous tubules, were present in all animals of the 300- and 600-mg/kg/day groups after the 21-day dosing period. Testes weight decreased and liver weight increased in these animals. Testes changes were dose-related and generally more severe among animals dosed orally versus intravenously. In the recovery animals, a residual DEHP-induced decrease in seminiferous tubule diameter was present in the testis of several animals dosed orally at 300 and 600 mg/kg/day, but not in animals dosed intravenously. There was no germinal cell depletion or Sertoli cell alteration observed in any dose group at any time. Notably, no effects on sperm count, sperm morphology, or sperm motility were observed at 90 days of age in any of the groups.
A 90-Day Oral Gavage Toxicity Study of d-Methylphenidate and d, I-Methylphenidate in Beagle Dogs
Authors: Teo Steve K. , Stirling David I. , Thomas Steve D. , Evans Mark G. , Khetani Vikram D.
Published: September 2003

d-Methylphenidate ( d-MPH) was approved as a treatment for attention deficit hyperactivity disorder (ADHD) in children. The repeated-dose toxicity of the d enantiomer of d, l-methylphenidate ( d, l-MPH) was assessed in male and female Beagle dogs. Dogs were orally dosed twice a day in equally divided doses 6 hours apart for total daily doses of 1, 3, and 10 mg/kg/day d-MPH or 20 mg/kg/day d, l-MPH for 90 days, followed by a 30-day recovery period. The top d-MPH dose of 10 mg/kg was equimolar to 20 mg/kg d, l-MPH in d-MPH content. The 10-mg/kg d-MPH and d, l-MPH doses were at least 13 times the maximum therapeutic dose giving rise to systemic exposures that were equivalent to or at least 2 times greater than those at the maximum therapeutic doses in children. The 10-mg/kg d-MPH and 20-mg/kg d, l-MPH doses had systemic exposures that were equivalent to or two to five times greater than the maximum therapeutic plasma levels in children respectively. There was no treatment-related mortality in all doses tested. Reversible salivation, hyperactivity, and diarrhea were seen in the high-dose d-MPH and d, l-MPH groups. Significant body weight loss and reduction in food consumption were observed in males for both high-dose groups with weights comparable to control values by the end of the recovery period. There were no abnormal clinical pathology or macroscopic or microscopic findings. Based on body weight changes, the no-observed-adverse-effect level (NOAEL) of d-MPH in beagle dogs was 3 mg/kg/day.