bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methods for Route-To-Route Extrapolation of Dose
Authors: Pepelko William E. , Withey James R. 
Published: September 2013

Results of acute toxicity studies for a variety of chemicals have indicated that, in most cases, although the inhalation route was more effective than the IG route, wide variations in toxicity occurred between these two routes. The major factors that may result in variations in toxicity between routes include: (1) differences in absorption efficiency; (2) differences in systemic effects; (3) occurrence of critical toxicological effects at the portal of entry; (4) first-pass effects resulting in inactivation or activation of the chemical agent before it reaches the target organ; and (5) variations in temporal patterns of target organ concentrations. Extrapolation to determine safe exposure levels during chronic exposure becomes less reliable, not only as information relating to these factors decreases, but also as the quality or length of exposure decreases in the available toxicologic studies. VDC is an example of one of a few chemicals for which both chronic inhalation and oral toxicity data are available, along with detailed pharmacokinetic information. On the basis of the pharmacokinetic data, differences in toxicity between the two routes did not appear to be very likely for this chemical. This conjecture was supported by the results of chronic toxicity studies. Finally, assuming sufficient data and pharmacokinetic parameters are available, this paper presents a useful and practical approach to route extrapolation.
Permissible Concentrations of Chemicals in Air and Water Derived From Rtecs Entries: a "Rash" Chemical Scoring System
Authors: Jones Troyce D. , Walsh Phil J. , Zeighami Elaine A. 
Published: September 2013

Many chemicals are of concern to human health, but only a few have epidemiologically derived risk estimates. About 45,000 chemicals are listed in RTECS, most of which have had some testing in subhuman models. RTECS entries range from cellular effects through organoleptic damage to lethality, with many pathological endpoints listed, including mutagenic changes, irritation, teratogenesis, cancer, mortality, etc. However, it is difficult to extend any biological test results to human risk assessments. If the results are extended, the degree of validity is highly uncertain. This paper describes a logical basis for using the entire complex spectrum of test results to evaluate the overall toxicological potency of a chemical to be assayed ( i.e., an interviewing chemical) and describes how to derive tentative, permissible concentrations in air and water for any particular chemical for which no regulatory guidance exists. This approach has been tested for 16 reference chemicals discussed in NIOSH Criteria Documents, EPA-CAG reports, etc. The evaluations are uncomplicated, but occasionally it is difficult to match RTECS entries for two different chemicals. Difficult compar isons may require some familiarity with experimental design and the toxicological literature. One important product of this novel approach is that a distribution or array of potency values is obtained for any chemical evaluated. This distribution reflects many uncertainties stemming from low statistical power, experimental design, pharmacological processes, interspecies variability, dose rate, biological effect monitored, route of treatment, etc. The array of relative values for a particular chemical reflects many different biological and physical conditions. The distribution of the array helps to index a composite toxicological profile for many different biological effects resulting from numerous treatment protocols. To minimize the effect of extreme sensitivity of certain (perhaps novel) biological test models, possible errors in the RTECS database, and possible human pharmacological insensitivity to a particular chemical and/or a particular route of administration, we consider the interquartile range (i.e., the central 50%) of the array of relative potency values between two chemicals being compared as a practical measure of uncertainty. Thus, the range in response derived from variability in relative potency should be useful in addressing the range of response in man as estimated from extrapolations of test data.
An Assessment and Quantitative Uncertainty Analysis of the Health Risks to Workers Exposed to Chromium Contaminated Soils
Authors: Paustenbach Dennis J. , Meyer Deborah M. , Sheehan Patrick J. , Lau Virginia 
Published: September 2013

Paustenbach, Dennis J., Deborah M. Meyer, Patrick J. Shee han, and Virginia Lau (1991). An assessment and quantitative uncertainty analysis of the health risks to workers exposed to chromium contaminated soils. Toxicol. Industrial Health. Millions of tons of chromite-ore processing residue have been used as fill in various locations in Northern New Jersey and else where in the United States. The primary toxicants in the residue are trivalent chromium [ Cr(III)] and hexavalent chromium [ Cr(VI)]. The hazard posed by Cr(III) is negligible due to its low acute and chronic toxicity. In contrast, Cr(VI) is considered a inhalation human carcinogen at high concentrations. Approxi mately 40 commercial and industrial properties in Northern New Jersey have been identified as containing chromite ore processing residue in the soil. One site, a partially-paved trucking terminal, was evaluated in this assessment. The arithmetic mean and geo metric mean concentrations of total chromium in soil were 977 and 359 mg/kg, respectively. The data were log-normal distrib uted. The arithmetic mean and geometric mean concentrations of Cr(VI) in surface soil were 37.6 and 3.1 mg/kg, respectively. The data could not be fit to a standard distribution, likely due to the large number of samples with concentrations below the method detection limit (65%). Dose was calculated for each exposure route using a Monte Carlo statistical simulation.
Environmental Impact Assessment as a Tool for Risk Management
Authors: Ratanachai Chatchai 
Published: September 2013

Environmental Impact Assessment is essentially a process comprising four elements: identification, prediction, evaluation, and monitoring. Properly conducted EIA studies can identify linkages between injurious events and/or activities and their damaging consequences. This aids in making the risk management decision. This paper discusses how EIA can be used as a tool for risk managemnet. Each element of EIA, as well as available risk management options, is discussed. As a case example, the paper reviews EIA guidelines/procedures in Thailand and identify weakness and strength in capabilities to identify the sensitive areas where risk should be effectively controlled.
Oxisterol Determination in Selected Coffees
Authors: Turchetto Edoardo , Lercker Giovanni , Bortolomeazzi Renzo 
Published: September 2013

The main aim of green-coffee processing techniques, such as decqffeination and roasting, is always to maintain a very high level of quality in taste and flavor, the beverage's most important cliaracteristics to consumers. Oxidative alterations of coffee lipids, which can occur in roasting, exert a very marked influence on these quality traits. Determining the extent of oxidation thus can provide an indication of the product's potential shelf-life and reveal traces of any newly-formed oxidative products that might prove nutritionally unsafe. Yet, while much attention has recently been focused on certain by-products induced by cholesterol oxidation and their proven toxicity as risk factors in atherosclerosis and cancer, oxidated phytosterols have largely gone unnoticed, being considered along with β-sitosterol as not very dangerous in that neither is absorbed by the intestinal tract. The present study investigates the substances derived from phytosterol oxidation (oxisterols) in samples of regular and decaffeinated commercial coffees. The findings show that oxisterols were absent in some samples and that the traces of oxidate phytosterols detected in others were well below the threshold considered as toxicologically active.
Rapid Assay of Cytotoxicity Using Tetramitus Flagellates
Authors: Jaffe Robert L. 
Published: September 2013

A simple test for measuring cytotoxic agents has been developed using the flagellate phenotype of Tetramitus rostratus. The test measures dose-dependent inhibition of cell division by individual agents such as 4-nitroquinoline-N-oxide and other mutagens. Dose-response data are given also for mixtures including coal tar pitch condensate, centrifuged particles obtained from tap water, and water concentrates prepared with XAD-2 resin. Because Tetramitus flagellates have a gullet and are particle-feeders, the assay allows for cytotoxic measurements of whole particles without prior extraction or solvent substitution procedures. The cytotoxic activities observed may reflect genotoxic activity, since all chemicals that produced a positive response are genotoxic in other test systems.
Michigan's Fisheater Cohorts: a Prospective History of Exposure
Authors: Humphrey Harold E.B. , Budd Marvin L. 
Published: September 2013

Interest in environmental contaminants and their effect on human health emerged as a primary focus in the 1970s following the discovery of significant levels of mercury, dichloro diphenyl trichloroethane (DDT), and polychlorinated bihpenyls (PCBs) in recreationally caught Great Lakes fish. In response to these findings, the Michigan Department of Public Health, in 1971, initiated a series of "fisheater" cohort studies. These studies continue to be conducted today. The evolution of human exposure assessment by serum PCB determination parallels the evolution of more precise and sensitive analytical laboratory procedures over the past 25 years. Early work quantitated PCB with Aroclor 1254 standards. By 1980, the Webb and McCall packed-column method (Webb and McCall, 1972, 1973), which quantitates total PCB with Aroclor 1016 and 1260 standards, had gained the Association of Official Analytical Chemists (AOAC) approval and became the accepted method. This method was used in the 1978-1980 Michigan Great Lakes Fisheater Study, the first sizable study of this kind in the nation. The study confirmed that fisheaters had significantly more exposure (median 21.4 ppb vs 6.6 ppb) than controls. Toxicology studies have indicated the need to quantitate individual PCB congeners, in order to correlate exposure with possible toxicological and health outcomes. Today, capillary column gas chromatography and gas chromatography/mass spectrometry are used to search for trace components of the total PCB dose (Mullen et al., 1984). Because of the legacy of the earlier analytical data, Michigan also continues to conduct packed-column analysis for longitudinalcomparisons. The Michigan fisheater study database and registry provide a significantly exposed and historic foundation for research testing health outcome hypotheses.
Environmental Contaminants and Reproductive Abnormalities in Wildlife: Implications for Public Health?
Authors: Guillette Louis J. , Guillette Elizabeth A. 
Published: September 2013

At the onset of the industrial age, environmental contaminants began to pose a major threat to the health of wildlife. That threat appears to continue today. In the last three decades, the focus of our concern on the health consequences of environmental pollution has been on lethal, carcinogenic, and/or extreme teratogenic manifestations. Evidence from a number of sources suggests that another mechanism, endocrine-disruption, also must be examined. There is excellent laboratory and field evidence that man-made chemicals (xenochemicals) released into the environment act as hormones or antihormones. They act as endocrine-disrupting contaminants (EDCs). The release of EDCs occurred in the past and continues today. The development of the reproductive system is vulnerable to perturbation by EDCs. Wildlife studies demonstrate that both sexes are affected and experience modifications of gonadal and reproductive tract development or functioning and abnormal synthesis or metabolism of hormones. A number of abnormalities seen in the reproductive system of various wildlife species correlate with similar abnormalities described as rising in human populations. We suggest that wildlife are excellent sentinels of ecosystem health. Data from these wildlife studies present models and methodologies for examining human health.
Minimizing Cancer Risk Using Molecular Techniques: a Review
Authors: Vojdani Aristo , Ghoneum Mamdooh , Choppa Paul 
Published: September 2013

This review article summarizes molecular markers that can signal enhanced risk of cancer and provide clinicians with these clues in order to attempt the use of natural and synthetic compounds to intervene in the early precancerous stages of carcinogenesis before invasive disease begins. With an aim such as this in mind, we have begun to apply molecular techniques based on many research articles to look for biomarkers capable of signaling a greater risk of cancer. It is possible to attain relatively quick answers by monitoring selected signs and damage in the body which provide the environment for abnormal cell growth and differentiation. These molecular techniques aim to uncover critical precancerous events taking place inside the body and identify measurable biologic flags signaling their occurrence. For years now, scientists have understood that the onset of cancer is a gradual, step wise process that may unfold over the course of decades, rather than a single, fixed event that can be dated in a pathologist's report. Carcinogenesis usually encompasses the prolonged accumulation of injuries at several different biological levels and includes both genetic and biochemical changes in cells. At each of these levels there is an opportunity for intervention—a chance to prevent, slow or even halt the gradual march of healthy cells toward malignancy. It is estimated that 75% of cancers are induced by chemicals; thus, if exposure to chemicals is avoided, cancer can be prevented. Also, depending on the individual's genetic background, the ability to metabolize chemicals is different among the population. This means that, "you and I can be exposed to exactly the same amount of a chemical, " yet our response will differ because we metabolize carcinogens differently due to different rates of deoxyribonucleic acid (DNA) repair, apoptosis, and mitosis or different levels of Phase I and Phase II detoxification enzymes. This, along with a more or less efficient immune system, may promote tumor formation or destroy a cancer cell at its earliest stage of development. Therefore, measurement of the biologic markers such as DNA and protein adducts, DNA damage, programmed cell death, DNA repair system, mitosis, gene activation, levels of antioxidants and efficient immune function described in this chapter and summarized in Figures 2 and 10, are biological clues indicating that the body has been assaulted by toxic (or cancer-causing) agents. This early identification of biomarkers for special vulnerability to the effects of chemicals and detection of selected signs of precancerous damage in the body may culminate preventive measures and the saving of lives.
Two New Cases of Liver Angiosarcoma: History and Perspectives of Liver Angiosarcoma Among Plastic Industry Workers
Authors: Hozo Izet , Andelinovi Šimun , Ljuti Dragan , Bojic Lovre , Miri Dinko , Giunio Lovel 
Published: September 2013

In this report of two new cases of liver angiosarcoma (ASL) among plastic industry workers, the authors present the history and perspectives of this problem. The first cases of ASL have been registered since 1974, and in 1984, the European register of angiosarcoma was founded. In this register, 11 cases of ASL and one case of haemangiopericytoma have been registeredfrom Croatia, all from a single plastics plant near Split. Two new cases ofASL (in retired autoclave cleaners, who were exposed to a concentration of 500-1000 ppm vinyl chloride monomer (VCM) during the working process) in the same plant are presented. They were detected with combined techniques ofASL detection, and both are still alive. The diagnoses have been histologically confirmed: one of them was surgically treated with segmental liver resection. The appearance of new cases of ASL confirms the perspective presented in the last report by the same authors.
Serum Levels of Several Organochlorine Pesticides in Farmers Correspond With Dietary Exposure and Local Use History
Authors: Brock John W. , Melnyk Lisa J. , Caudill Samuel P. , Needham Larry L. , Bond Andrew E. 
Published: September 2013

In response to reported increased cancer risks among farmers, the Agricultural Health Study (AHS) was designed to examine health outcomes and environmental exposures among farm families in the United States. In the pilot phase of the AHS, food, beverage, air, dermal, dust, surface wipe, and biological specimens (blood and urine) were collected and analyzed for six farm families in two states (IA and NC). In addition, questionnaires were administered to examine previous pesticide use. This paper reports the organochlorine pesticide results of the serum and dietary analyses as well as questionnaire results from the pilot exposure study of farmers and their families. Note, no organochlorine pesticides were reported as currently being applied to the study farms. In all human serum samples examined, typical U.S. population levels were found for the majority of the pesticides. In addition, human serum levels of organochlorine pesticides showed no significant daily or seasonal variation. However, serum trans-nonachlor levels were found to be higher in people living on the two farms in North Carolina than
Unchanging Incidence of Hip Fracture in Southeastern Norway
Authors: Polesie Sam , Sigurdsen Ulf , Bjørgul Kristian 
Published: September 2013

Purpose: The aim of this study was to ascertain trends in the incidence of hip fracture in southeastern Norway by comparing the hip fracture incidence for the years 2008 to 2010 to that of a study from 1998 to 2003 in the same area. Methods: We determined the number of hip fractures for the geographical area of Ostfold county, and the age- and gender-specific incidence per 100 000, with 95% confidence intervals, was calculated. Use of bisphosphonates was determined by extracting data from public databases. Results: The hip fracture incidence for men aged 50 to 74 and older than 75 years was 120 (100-141) and 1305 (1237-1372) in the latest time period, 1998-2003, whereas the incidence for the previous period, 2008-2010, was 124 (103-146) for men aged 50 to 75 and 1333 (1189-1476) for men older than 75 years. For women of 50 to 74 years, the incidence was 184 (158-209), and for women older than 75 years, it was 2523 (2428-2618). In the first time period, the corresponding incidence was 228 (200-257) for women aged 50 to 74 and 2330 (2189-2471) for women older than 75 years. As the 95% confidence intervals overlap in all the comparisons, it indicates the the incidence did not significantly differ between the time periods. Bisphosphonate use did not exceed 2% in any age group for men. For women, the highest rate of bisphosphonate use was 12.6% in the 85- to 89-year groups. Conclusion: We cannot confirm reports of decreasing incidence of hip fracture
Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification
Authors: Ott German , Rosenwald Andreas , Campo Elias 
Published: September 2013

AbstractMYC is a potent oncogene initially identified as the target of the t(8;14)(q24;q32) chromosome translocation in Burkitt lymphoma. MYC gene alterations have been identified in other mature B-cell neoplasms that are usually associated with an aggressive clinical behavior. Most of these tumors originate in cells that do not normally express MYC protein. The oncogenic events leading to MYC up-regulation seem to overcome the inhibitory effect of physiological repressors such as BCL6 or BLIMP1. Aggressive lymphomas frequently carry additional oncogenic alterations that cooperate with MYC dysregulation, likely counteracting its proapoptotic function. The development of FISH probes and new reliable antibodies have facilitated the study of MYC gene alterations and protein expression in large series of patients, providing new clinical and biological perspectives regarding MYC dysregulation in aggressive lymphomas. MYC gene alterations in large B-cell lymphomas are frequently associated with BCL2 or BCL6 translocations conferring a very aggressive behavior. Conversely, MYC protein up-regulation may occur in tumors without apparent gene alterations, and its association with BCL2 overexpression also confers a poor prognosis. In this review, we integrate all of this new information and discuss perspectives, challenges, and open questions for the diagnosis and management of patients with MYC-driven aggressive B-cell lymphomas.
Transitions between Andean and Amazonian centers of endemism in the radiation of some arboreal rodents
Authors: Upham Nathan S , Ojala-Barbour Reed , Brito M Jorge , Velazco Paúl M , Patterson Bruce D 
Published: September 2013

Abstract

Background
The tropical Andes and Amazon are among the richest regions of endemism for mammals, and each has given rise to extensive in situ radiations. Various animal lineages have radiated ex situ after colonizing one of these regions from the other: Amazonian clades of dendrobatid frogs and passerine birds may have Andean ancestry, and transitions from the Amazon to Andes may be even more common. To examine biogeographic transitions between these regions, we investigated the evolutionary history of three clades of rodents in the family Echimyidae: bamboo rats (Dactylomys-Olallamys-Kannabateomys), spiny tree-rats (Mesomys-Lonchothrix), and brush-tailed rats (Isothrix). Each clade is distributed in both the Andes and Amazonia, and is more diverse in the lowlands. We used two mitochondrial (cyt-
b and 12S) and three nuclear (GHR, vWF, and RAG1) markers to reconstruct their phylogenetic relationships. Tree topologies and ancestral geographic ranges were then used to determine whether Andean forms were basal to or derived from lowland radiations.

Results
Four biogeographic transitions are identified among the generic radiations. The bamboo rat clade unambiguously originated in the Amazon ca. 9 Ma, followed by either one early transition to the Andes (Olallamys) and a later move to the Amazon (Dactylomys), or two later shifts to the Andes (one in each genus). The Andean species of both Dactylomys and Isothrix are sister to their lowland species, raising the possibility that highland forms colonized the Amazon Basin. However, uncertainty in their reconstructed ancestral ranges obscures the origin of these transitions. The lone Andean species of Mesomys is confidently nested within the lowland radiation, thereby indicating an Amazon-to-Andes transition ca. 2 Ma.

Conclusions
Differences in the timing of these biogeographic transitions do not appear to explain the different polarities of these trees. Instead, even within the radiation of a single family, both Andean and Amazonian centers of endemism appear enriched by lineages that originated in the other region. Our survey of other South American lineages suggests a pattern of reciprocal exchange between these regions—among mammals, birds, amphibians, and insects we found no fewer than 87 transitions between the Andes and Amazon from Miocene-Pleistocene. Because no clear trend emerges between the timing and polarity of transitions, or in their relative frequency, we suggest that reciprocal exchange between tropical highland and lowland faunas in South America has been a continual process since ca. 12 Ma.