bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Composite Model for Multiple Assays of Skin Irritation
Authors: Cruzan George , Dalbey Walden E. , D'Aleo Christopher J. , Singer Edward J. 
Published: September 2013

A model for skin irritation was developed for simultaneous evalua tion of the influence on irritation of abrasion, occlusion, and dura tion of treatment and for fulfillment of requirements for labeling considerations under DOT, CPSC-FHSA, OSHA, and EEC. This model greatly reduces the number of animals required to address submissions under multiple agencies compared to performing each test separately. In this model, which we have called a Composite Skin Irritation test, a test material is placed on three pairs of intact and abraded sites on each rabbit; one pair of sites is occluded for 4 hours, one for 24 hours, and the other left unoccluded for 24 hours. Results are presented from 88 composite tests with 80 petroleum- related materials. For the materials tested, abrasion of the skin had no effect on the irritation response. Occlusion of the test site gener ally did not result in dramatic increases in response, except for petroleum refinery streams with a boiling range below 500° F. Exposure for 4 hours rather than 24 hours generally resulted in less irritation; however, for individual compounds, -the irritation from the 4-hour exposure could not be predicted from the response to the 24-hour exposure. Of the 80 materials tested, 12 would be labeled as skin irritants under CPSC guidelines, three under OSHA, and 20 under EEC. Of the 20 that would be labeled under EEC criteria, only seven would be labeled under CPSC criteria. At least for petroleum-related materials, results from skin irritation studies performed under one set of conditions cannot be used to predict the degree of irritation that would be produced under a dif ferent set of exposure conditions.
The Use of Multivariate Analysis To Compare Peroxisome Induction Data On Phthalate Esters in Rats
Authors: Lin Lawrence I-Kuei 
Published: September 2013

This paper contains statistical evaluations of the effect of 9 different plasticizers on rat hepatic peroxisome proliferation. There were 9 21-day feeding studies with one plasticizer in each study. The plasticizers are: di(2-ethylhexyl)phthalate (DEHP), butyl benzyl phthalate (BBP), 711 phthalate (711P), di(n-butyl)phthalate (DBP), di(undecyl)phthalate (DUP), di(isodecyl)phthalate (DIDP), di(isononyl)phthalate (DINP), 610 phthalate (610P), and di(ethylhexyl)adipate (DEHA). For each plasticizer, several dosage (as % of diet) groups, plus a negative control group (0%) and a reference control group (1.2% DEHP) were included. There were 5 males and 5 females, approximately 5 weeks old, per group per plasticizer, for a total of 470 animals. For each animal, body weight and food intake ivere measured prior to treatment and twice a week during the treatment period. Animals were necropsied at the end of the 21-day treatment period. Selected organs and blood samples of each animal were collected for measuring hepatic enzymes, proteins, fat stains, organ weights and serum fats. The endpoints included electron microscopy examination of liver peroxisome proliferation and liver histological abnormalities. The statistical evaluation utilized a multivariate approach that condensed a cornplex phenornenon into certain meaningful and simple endpoints for quantitative comparisons. The dose of each plasticizer that would protect 99% and 99.9% of rats against peroxisome proliferation (xx% statistically predicted dose, or xx% SPD) was estimated. Marked differences were seen in the ability of the 9 test conipoziilds to cause hepatic peroxisome proliferation in rats. The graphic ranking of overall potency is, in order from most potent to least potent: DEHP, DIDP, DINP, DBP, DEHA, DUP, BBP, 711P and 610P. The ranking in terms of 99.9% SPD is: DEHP, DINP, DIDP, DBP, 610P, DUP, DBP, 711P and DEHA. It was also found that the histological findings of reduced basophilia or increased eosinophilia were highly correlated with peroxisome proliferation (r = 0.94). The other histological findings were incidental observations for specific plasticizers.
A 90-Day Toxicity Study of the Effects of Petroleum Middle Distillates on the Skin of C3H Mice
Authors: Freeman James J. , Mckee Richard H. , Phillips Richard D. , Plutnick Robert T. , Scala Robert A. , Ackerman Larry J. 
Published: September 2013

Petroleum middle distillates (PMDs) elicit skin tumors in mouse epidermal carcinogenesis studies. The response is characterized by a long latency with only a small percentage of animals developing tumors. Although the carcinogenic activity of certain other petroleum hydrocarbons largely depends upon the presence of polycyclic aromatic hydrocarbons (PAHs), many PMDs contain relatively low concentrations of PAHs. PMDs are also irritating to mouse skin, and chronic irritation may be involved in the development of skin tumors. This study was conducted to investigate the patterns of cutaneous irritation elicited by topical application of PMDs having compositional differences. The three PMDs selected for study were a steam cracked gas oil (SCGO), a lightly refined paraffinic oil (LRPO), and a jet fuel (JF). Male C3H/HeNCr1BR mice (25/group) were treated topically (37.5 μl 2x/week for 13 weeks) with 10%, 50% or 100% (undiluted) concentrations of each PMD. Catalytically cracked clarified oil (CCCO, 10%), a potent carcinogen to mouse skin, was also tested. The vehicle was a noncarcinogenic mineral oil with a viscosity of 90 SUS. Cutaneous changes were evaluated by gross observations and light microscopy. Cutaneous irritation was the only significant toxic response in this study. Neither the vehicle nor any of the 10% PMD concentrations produced significant cutaneous irritation. The 10% CCCO and 50% PMD treatments all elicited slight to moderate proliferative and inflammatory changes in mouse skin. Ulcers were also observed microscopically in mice treated with 10% CCCO and 50% SCGO. The 100% SCGO treatment produced evidence of necrosis on Days 1–7 but not later in the study despite continued treatment. In contrast, the irritating effects of 100% LRPO were not evident until 2–3 weeks of study, and at study completion were characterized by moderately severe inflammatory and proliferative changes. The effects of 100% JF were qualitatively similar to 100% LRPO but less marked. Thus, the SCGO caused a different pattern of cutaneous responses than either LRPO or JF. The possible relationships of these cutaneous changes to epidermal carcinogenesis are being studied further.
Liver Carcinogenesis is Not a Predicted Outcome of Chemically Induced Hepatocyte Proliferation
Authors: Melnick Ronald L. , Huff James 
Published: September 2013

Cell proliferation has long been recognized as a basic component of multistage carcinogenesis. Based largely on the finding that certain nongenoloxic chemical carcinogens induce cell proliferation in the same organ that develops tumors after long-term exposure, some suggest that the increased rates of cell division account for the carcinogenicity of these chemicals. This paper examines relationships between chemically induced liver toxicity, cell proliferation, and liver carcinogenesis; major factors include consistency, transient vs. sustained dose-response correspondence, and scientific plausibility. For a presumed mechanism to be valid, a sustained proliferative response is critical, largely because transient increases in hepatocyte proliferation are not sufficient to induce cancer or promote liver tumor development. A consistent association between liver toxicity and carcinogenicity has not been established. Our evaluation of studies on purported relationships between chemically induced cell proliferation and liver carcinogenesis shows: 1) that inconsistencies in sex and species specificity exist, 2) that a large percentage of proliferative responses are transient, 3) that inconsistencies in response to various hepatic peroxisome proliferators are common, and 4) that dose-response and duration relationships have not been sufficiently examined. Studies of proliferative responses of putative preneoplastic cells in the liver indicate that these cells divide faster than normal hepatocytes and also have higher death rates. Chemicals that induce cell proliferation in preneoplastic foci do not always provide a persistent increase in replication rates, even with continuous exposure. A selective growth advantage to preneoplastic cells in the liver may be provided either by an enhancement of the replication rates of these cells compared to the surrounding normal hepatocytes, by inhibition of cell loss, or by inhibition of the growth rate of normal cells. More work is needed to understand how chenvcal carcinogens and noncarcinogens affect cell division and cell loss of normal hepatocytes and of preneoplastic cells; measurements of hepatocyte proliferation alone are not sufficient to elucidate mechanisms of liver tumor development or to predict liver carcinogenesis. Because of our limited knowledge of the complex molecular changes occurring during liver cancer, it would be inappropriate and far too premature to amend scientific risk assessment procedures for nongenotoxic chemical carcinogens based on oversimplified or incompletely tested speculations.
Suppressed Natural Killer Cell Activity in Patients with Silicone Breast Implants: Reversal upon Explantation
Authors: Campbell Andrew , Brautbar Nachman , Vojdani Aristo 
Published: September 2013

We have previously shown that natural killer (NK) cell activity is significantly suppressed in patients with silicone breast implants. These patients were symptomatic and the suppression of natural killer cell activity was associated with additional significant immunological abnormalities (Vojdani et al, 1992a). Our studies have recently been confirmed by Smith et al. (1994), who described natural killer cell activity suppression following exposure to silicone gel, and reversal upon removal of the gel. This study has been designed to evaluate natural killer cell activities in symptomatic women with silicone breast implants and again after explantation of the implants. Each patient served as her own control. Our findings show a marked significant increase in previously suppressed natural killer cell activity in 50% of the patients. In the other 50%, no change or suppressed NK activity was observed. These findings are compatible with recent studies in experimental animals, which show that administration of silicone reduces natural killer cell activity, and that this is reversible upon removal of the silicone. Since NK cells are important in the control of tumor cell growth, we propose here that patients with reduced NK cell activity are at a higher risk of developing cancer, a concept recently described in experimental animals (Potter et al., 1994; Salhon et al, 1994).
Toxicological Investigations in the Semiconductor Industry
Authors: Schmidt Reiner , Scheufler Horst , Bauer Siegfried , Wolff Lona , Pelzing Matthias , Herzschuh Rainer 
Published: September 2013

The prenatal toxic effects of contaminated vacuum pump oil (Sample A) and solid waste products (Samples B and C) originating from aluminum plasma etching processes in semiconductor manufacturing were investigated. Three strains of pregnant mice with different degrees of sensitivity during organogenesis (days 6-15 of gestation) were treated daily with 1000 mg/kg b. w. (Sample A), 500 or 750 mg/kg b.w. (Sample B), and 250, 500, or 750 mg/kg b.w. (Sample C). On day 18 of pregnancy, the animals were killed and examined for gross changes, number and weight of live fetuses, as well as the number of postimplantation losses and malformations. Analytical data showed that the investigated wastes contained various halogenated hydrocarbons and inorganic compounds. Sample A revealed no signs of prenatal toxic action. In contrast, administration of Samples B and C caused strong prenatal toxic effects. The number of live fetuses declined in a dose-related manner, and evidence of intrauterine growth retardation was noted in fetuses that survived to day 18. The number of fetuses with malformations (only cleft palates) rose significantly in accordance with the doses and sensitivity of the strains (> 95% of the fetuses of the most sensitive strain after 750 mg/kg; 85% after 500 mg/kg).
Neutral Endopeptidase (NEP) and Its Role in Pathological Pulmonary Change With Inhalation Exposure To JP-8 Jet Fuel
Authors: Pfaff John K. , Tollinger Brian J. , Lantz R. Clark , Chen Huizhong , Hays Allison M. , Witten Mark L. 
Published: September 2013

Through a simulated flightline exposure protocol, Fischer 344 rats (F344) were subjected to an aerosol/vapor mix of the military jet fuel, JP-8. Previous studies with this model of lung injury have revealed significant increases in pulmonary resistance, increased alveolar clearance of 99mTcDTPA, and a decrease in bronchoalveolar lavage fluid (BALF) concentration of the neuropeptide substance P (SP). Exposures to JP-8 were nose-only and for one hour daily. Six groups of Fischer 344 rats were exposed for 7, 28, or 56 days at two JP-8 concentrations (low dose = 469-520 mg/m3/hr, high dose = 814-1263 mg/m3/hr). Exposed groups were matched with longitudinal controls. In response to JP-8 inhalation, exposure animals demonstrated a dose-dependent as well as duration-determined reduction in BALF SP concentration. Both JP-8 concentrations caused significant pathological changes in lower pulmonary structures. We designed this study to elucidate the cause of SP deficits following JP-8 inhalation through correlation with neutral endopeptidase (NEP) concentration taken from paired samples. NEP activity is significantly increased after 28 days of high-dose exposure (HD28) when compared with longitudinal controls and low-dose exposures (7D, 28D, and 56D). A significant inverse relationship between SP and NEP activity is demonstrated through Spearman rank-order correlation (rs = -0.42, n = 52, p < 0.05), suggesting inactivation of SP as the cause of its deficit. Pulmonary airway changes strongly implicate airway epithelium as a primary site of injury. Tachykinin degradation from the peptidase, NEP, plays a role in the process of airway cell injury. This research demonstrates the possible use of NEP and SP lung concentrations as biomarkers of chronic hydrocarbon exposure.
The Great Lakes: a Historical Overview
Authors: Hicks Heraline E. 
Published: September 2013

The Great Lakes are collectively the largest inland body of freshwater on this planet. For more than two hundred years, the Great Lakes basin has been used as a resource for industry, agriculture, shipping, and recreation. The physical characteristics of the basin and the long retention time of chemicals in the lakes combine to make this huge freshwater resource a repository for chemical by-products of these activities. Many of the more than one thousand chemicals detected in the waters, sediment, or biota of the Great Lakes have known toxic effects. This overview will identify the 11 most persistent toxic chemicals known as "critical" Great Lakes pollutants. It also will describe some of the adverse health effects that have been observed in fish and other wildlife because of exposure to these pollutants. Finally. it will discuss some of the early human health studies that 1) have demonstrated a correlation between increased body burdens and fish consumption, and 2) suggest an association between consumption of contaminated Great Lakes fish and adverse human health effects.
Harmonizing Human Health Studies in the Great Lakes
Authors: Hicks Heraline E. , Spengler Robert F. 
Published: September 2013

Epidemiological studies of exposed human populations can provide valuable evidence of human health effects. Information has been sparse on human health effects associated with consumption of contaminated Great Lakes fish. As part of its Great Lakes Human Health Effects Research Program, the Agency for Toxic Substances and Disease Registry (ATSDR) has funded ten projects. Of these studies, eight are epidemiologic investigations of human exposure and potential health effects from consumption of contaminated fish. To strengthen and to enhance the findings and comparability across the health studies, ATSDR has initiated several activities. These activities include harmonizing questionnaires, analytical protocols, human health end points, and contaminants tested. Also included is the establishment of a quality assurance and quality control (QA/QC) program and tissue bank. These activities will allow ATSDR to enhance exposure assessment in the Great Lakes basin. In addition, these research activities allow ATSDR to evaluate and to interpret data across all the projects, including a basin-wide health risk analysis on exposure, levels of contaminants or body burden, and the potential for human health effects from exposure to Great Lakes contaminants.
Adaptive evolution of the osmoregulation-related genes in cetaceans during secondary aquatic adaptation
Authors: Xu Shixia , Yang Yunxia , Zhou Xuming , Xu Junxiao , Zhou Kaiya , Yang Guang 
Published: September 2013

AbstractBackgroundOsmoregulation was a primary challenge for cetaceans during the evolutionary transition from a terrestrial to a mainly hyperosmotic environment. Several physiological mechanisms have been suggested to maintain the water and salt balance in cetaceans, but their genetic and evolutionary bases remain poorly explored. The current study investigated the genes involved in osmoregulation in cetaceans and compared them with their counterparts in terrestrial mammals to test whether adaptive evolution occurred during secondary aquatic adaptation.ResultsThe present study analyzed the molecular evolution of 11 osmoregulation-related genes in 11 cetacean species, which represented all of the major cetacean clades. The results demonstrated positive selection acting on angiotensin converting enzyme (ACE), angiotensinogen (AGT), SLC14A2, and aquaporin 2 (AQP2). This evidence for the positive selection of AQP2 and SLC14A2 suggests that the adaptive evolution of these genes has helped to enhance the capacity for water and urea transport, thereby leading to the concentration of urine, which is an efficient mechanism for maintaining the water balance. By contrast, a series of positively selected amino acid residues identified in the ACE and AGT (two key members of the renin-angiotensin-aldosterone system, RAAS) proteins of cetaceans suggests that RAAS might have been adapted to maintain the water and salt balance in response to a hyperosmotic environment. Radical amino acid changes in positively selected sites were distributed among most internal and terminal branches of the cetacean phylogeny, which suggests the pervasively adaptive evolution of osmoregulation since the origin of cetaceans and their subsequent diversification.ConclusionsThis is the first comprehensive analysis of the molecular evolution of osmoregulation-related genes in cetaceans in response to selection pressure from a generally hyperosmotic environment. Four genes, i.e., AQP2, SLC14A2, ACE, and AGT were subject to positive selection in cetaceans, which suggests that cetaceans may have adapted to maintain their water and salt balance. This also suggests that cetaceans may have evolved an effective and complex mechanism for osmoregulation.
Factors predicting mood changes in oral contraceptive pill users
Authors: Shakerinejad Ghodratollah , Hidarnia Alireza , Motlagh Mohammad Esmaeil , Karami Khodabakhsh , Niknami Shamsoddin , Montazeri Ali 
Published: September 2013

Abstract

Background
Over 100 million women worldwide are using oral contraceptives pills (OCP) and mood changes were being as the primary reason for OCP discontinuation. The purpose of this study was to determine the prevalence and predicting factors of mood changes in oral contraceptive pills users.

Methods
This was a cross-sectional study of 500 women aged 15–49 years old using low dose (LD) pills attending family planning centers in Ahwaz, Iran. Data were collected via face-to-face interviews using a structured questionnaire including items on demographic, self-efficacy and mood change. Both univarate and multiple logistic regression analyses were performed to assess the relationship between reported mood change and the independent variables.

Results
In all 406 women reported that they did experience OCP side effects. Of these, 37.7% of women (n =153) reported mood changes due to OCP use. The results of multiple logistic regression revealed that place of living (OR = 2.57, 95% CI = 1.06-6.20, p = 0.03), not receiving information on OCP side effects (OR = 1.80, 95% CI = 1.15-2.80, p = 0.009), and lower self-efficacy (OR = 0.87, 95% CI = 0.80-0.94, p = 0.001) were significant predictors of mood changes.

Conclusion
The findings from this study indicated that the prevalence of reported mood changes due to OCP use among Iranian women appeared to be consistent with other studies. In addition the findings showed that receiving information on OCP side effects from health care workers and self-efficacy were important predicting factors for mood changes. Indeed implementing educational programs and improving self-efficacy among women are recommended.
Clinical forum: canine localised adult-onset demodicosis
Authors: Wright Ian , Bate Simon , Mctaggart Donald , Cox Alistair 
Published: September 2013

Canine demodicosis: a case in practice This clinical forum considers a case of demodicosis encountered by the author in practice. The case raises particular challenges in terms of management and treatment options. A series of questions regarding this case were asked of specialists from different disciplines relevant to the case, and their views summarised.
Wilhelm Weinberg’s Early Contribution to Segregation Analysis
Authors: Stark Alan , Seneta Eugene 
Published: September 2013

AbstractWilhelm Weinberg (1862–1937) is a largely forgotten pioneer of human and medical genetics. His name is linked with that of the English mathematician G. H. Hardy in the Hardy–Weinberg law, pervasive in textbooks on population genetics since it expresses stability over generations of zygote frequencies AA, Aa, aa under random mating. One of Weinberg’s signal contributions, in an article whose centenary we celebrate, was to verify that Mendel’s segregation law still held in the setting of human heredity, contrary to the then-prevailing view of William Bateson (1861–1926), the leading Mendelian geneticist of the time. Specifically, Weinberg verified that the proportion of recessive offspring genotypes aa in human parental crossings Aa × Aa (that is, the segregation ratio for such a setting) was indeed p=14. We focus in a nontechnical way on his procedure, called the simple sib method, and on the heated controversy with Felix Bernstein (1878–1956) in the 1920s and 1930s over work stimulated by Weinberg’s article.
Biodegradation of Malachite Green by Extracellular Laccase Producing Bacillus thuringiensis RUN1
Authors: Olumide D. Olukanni  , Aliu Adenopo  , Ayodeji O. Awotula  , Akinniyi A. Osuntoki  
Published: September 2013

A bacteria strain Bacillus thuringiensis RUN1identifiedby 16s RNA gene phylogenetic analysiswas used to decolorize malachite green, a triphenylmethane dye in a simulated wastewater. The ability of the organism to produce extracellular laccase and degrade the dye were also investigated. Results showed that the organism decolorized (84.67 ± 1.19 %) malachite green at 40 mgl-1 within 6 h; and the decolorization was associated to laccase production by the organism experimentally. Laccase activity increased as the decolorization process progressed, with the highest activity value of 0.1043 ± 0.02 U/min/ mg protein recorded after 24 h of incubation using ABTS as substrate. In addition, FTIR analysis showed that the strain actually degraded the dye. It was therefore concluded that this strain of Bacillus thuringiensis will be relevant in the biotreatment of industrial effluent containing malachite green and in the production of laccase, an industrially important enzyme.