bluuebunny/crossref_metadata_2025 huggingface dataset:
Practical Procedure of Testing for Neurotoxicity
Authors: Schaeppi U. , Fitzgerald R. E.
Published: November 2007

In the course of routinely performed subchronic toxicity studies with laboratory rodents, functional neurotoxicity, i.e., behavioral changes, usually are noted first during the daily cageside observations of all animals, Observation and neurologic examination of a few key animals provide a tentative diagnosis. Subsequent automated testing procedures for further characterization and quantifying behavioral changes might include motor activity, startle response, hurdle stepping, and maze behavior. Automated testing serves to assess the no observable effect under conditions of blind testing and provides further refinement of the diagnosis. Behavioral changes should be assessed as early as possible after onset of testing, i.e., during acute tests for mortality and the subsequent subchronic range-finding studies. Subsequent subchronic organ toxicity studies are then carried out by following a validated experimental protocol, including automated testing procedures and appropriate neuropathologic evaluation.
Evaluation of Sensory System Function Using Reflex Modification of the Startle Response
Authors: Crofton K. M. , Sheets L. P.
Published: November 2007

Methods to measure damage to sensory systems after toxicant exposure vary from rapid and subjective tests (e.g., pinna reflex) to time-consuming and objective tests (e.g., psychophysical tests). Reflex modification of the startle response represents an alternative technique in the assessment of sensory function. Advantages of this procedure include no prior training requirements, rapid and objective measurement of sensory thresholds, ability to differentiate sensory from nonsensory damage, and potential for predictive validity. This procedure also has been shown to be sensitive to a variety of neurotoxic compounds. Future research should concentrate on demonstrating the research potential of this technique for use in neurotoxicology.
Screening for Neurotoxic Potential of Chemicals in the Federal Republic of Germany
Authors: Winneke Gerhard
Published: November 2007

The German Chemicals Act (Chemikaliengesetz) requires that new chemicals be tested for toxicity according to a stepwise procedure based on production quantities. If the expected total annual production exceeds 1,000 tons, screening for “behavior-disrupting properties” is required as part of chronic toxicity testing. A test guideline based on cageside observations was published in 1985. The protocol covers outer appearance as well as motor, sensory, and autonomic functions and signs indicative of central nervous system (CNS) functions. So far, no chemical has been screened for behavioral toxicity according to this guideline because the expected production quantities never exceeded the threshold required for chronic toxicity testing.
The New Occupational Physician—Necessity for Attention to Environmental Issues
Authors: Tsuchiya Kenzaburo
Published: November 2007

This short article emphasizes the necessity for occupational health physicians to pay closer attention to global environmental issues including risk assessment and risk management of those issues. Industrialization casts both light and shadow. Every effort should be made to balance the light and shadow, and where possible, to provide more of the former and lessen the latter. More experts in this field must be trained and hired as faculty at schools of medicine, particularly at schools or institutes offering training in occupational health.
Use of Pulmonary Macrophages in Metal Toxicity: A Brief Overview
Authors: Fisher Gerald L.
Published: November 2007

The pulmonary macrophage provides a critical function in the maintenance of the sterility and integrity of the lung. Inhaled particle deposited in the deep lung may interact directly with macrophages to manifest either primary cellular toxicity or secondary pulmonary damage resulting from impaired macrophage function. The advantages and disadvantages of in vitro macrophage culture systems as predictors of in vivo pulmonary toxicity are briefly described. Recommendations are presented for areas of additional research as well as effective utilization of this assay system.
Zinc Toxicity: Does It Exist?
Authors: Léonard A. , Gerber G. B.
Published: November 2007

Zinc is an indispensable trace element and is a constituent of more than 200 enzymes. It can assure the stability of biological molecules such as DNA, or biological structures such as membranes or ribosomes. It is not surprising, therefore, that, compared with zinc toxicity, zinc deficiency is a much more frequent risk. Few acute toxic effects have been ascribed to zinc and no long-term effects were found after single or prolonged exposure at doses below 1 g/kg of food. Zinc is neither mutagenic nor carcinogenic, although its levels may influence tumor growth. Zinc appears not to be teratogenic but, on the contrary, deleterious action on zinc deficiency on the developing organisms is well documented.
Mercury
Authors: Clarkson Thomes W.
Published: November 2007

New findings on the environmental fate of Hg indicate that lakes can be contaminated by long distance transport on mercury vapor in the atmosphere and that higher levels of Me Hg in fish are associated with acidification of lakes and with the creation of hydroelectric reservoirs. Considerable progress has been made in the understanding of the disposition and metabolism of mercury in the body. Inhaled mercury vapor rapidly enters cells in view of its lipid solubility. Inside the cell, it is oxidized by the enzyme, catalase, to inorganic divalent mercury. The latter may be the proximate toxic species. Me Hg also crosses cell membranes rapidly but, in this case, probably by forming water-soluble complexes whose structures mimic those of endogenous substrates that are transported on specific carriers.

The mechanism of damage to the central nervous system by mercury vapor is still unknown. The kidney damage probably arises from the effect of inorganic mercury on immunocompetent cells causing them to produce antibodies that affect the glomerulus. The selective damage by Me Hg to specific anatomical areas of the brain and the long latent period are still unexplained. Most studies have focused on the earliest biochemical lesion, the inhibition of protein synthesis. Prenatal damage occurs in all areas of the developing brain. Cell division and abnormal neuronal migration are the processes primarily affected. The destruction of microtubules in neuronal and astrocystic cells offers a plausible explanation of the deranged cytoarchitecture. Prenatal effects such as delays in the normal development of prenatally exposed infants occur at exposures substantially lower than those associated with the onset of adult poisoning.
Hormonal Evaluation of Testicular Function: Species Variation
Authors: Nett Terry M.
Published: November 2007

Many hormones are involved in regulation of the testis. Some of these act directly on the testis itself, while others act indirectly by influencing secretion or clearance of those that may act on the testis. Methods are not yet available for easily quantifying some of the hormones that affect testicular function, such as growth factors. Most hormones are secreted as pulses rather than in a constant, continuous manner. This necessitates appropriate sampling regimens to define the amplitude and frequency of the pulses. Factors such a stress, changes in environmental conditions, level of nutrition, and disease may alter the pattern and rate of secretion of hormones that regulate testicular function. All of these factors must be considered when designing experiments to determine how drugs affect the function of the testis.
Epidemiology and Toxicology of Volatile Organic Chemical Contaminants in Water Absorbed Through the Skin
Authors: Thomas Richard D.
Published: November 2007

This paper provides a general introduction to the occurrence, epidemiology, and toxicity of some of the most common contaminants of water supplies, the volatile organic chemicals (VOCs). The VOCs are formed from the reaction of chlorine during disinfection with naturally occurring carbon in the form of humic acids. The VOCs may also enter water supplies as a result of manufacturing, processing, distribution, and urban and agricultural run off. Their occurrence is summarized in this paper.

No epidemiologic studies examine the health effects where skin is the sole route of exposure. However, in several studies skin is one of the routes of exposure for VOCs. These are summarized in this paper.

Finally, the toxicity of some of the more important VOCs is summarized. Where possible, similarities in toxicity between individual members of this class of chemical contaminants are noted. There are striking similarities of toxicity of various VOCs in the liver, kidney, and hematopoietic system. These similarities should be considered as skin exposure models are being developed.
Use of Percutaneous Absorption Data in Risk Assessment
Authors: Franklin C. A. , Somers D. A. , Chu I.
Published: November 2007

Assessment of risks to humans associated with the use of chemicals requires knowledge of the hazard (toxicity) of the chemical and level of human exposure. Hazard assessment is often based on animal bioassays and quantitative exposure estimates of dermal exposure obtained from studies monitoring workers. Because human skin is an effective barrier to many chemicals, it cannot be assumed that the deposited dose is equivalent to the systemic dose. However, an estimate of systemic dose may be derived by multiplying the deposited dose by the percentage of percutaneous uptake. This correction can have major impact on the regulatory decision, because the adjusted dose used in the risk calculation may be reduced significantly, especially at high doses, when the uptake is not linearly proportional to the exposure. It is therefore important that the dermal absorption value be accurate. As outlined in this paper, numerous factors can affect percutaneous absorption. Nevertheless, many regulatory agencies will consider the use of percutaneous absorption data derived from in vivo studies to adjust the dermally deposited dose to that delivered systemically. Numerous issues must be resolved before in vitro dermal penetration studies can be used for risk assessment.
Assessing Community Exposure to Selected Volatile Indicator Compounds
Authors: Lagrone F. Scott
Published: November 2007

This paper is summarized from a report prepared by the Houston Regional Monitoring Corporation for submission to the U.S. Environmental Protection Agency explaining the methodology used in the East Harris County and West Chambers County for assessing community exposure to volatile compounds. The paper briefly discusses the program description, the rationale for selecting candidate airborne chemicals for detailed health effects assessments, and the method used to develop consensus guidance values based on accepted risk assessment methodologies. The results of a 6-month monitoring period are presented with health assessment indicators.
Health Effects of Ozone Depletion
Authors: Kripke Margaret L.
Published: November 2007

The problem of ozone depletion has recently become a topic of major concern. What was once a vague, theoretical hypothesis that artificial chlorofluorocarbon compounds could accumulate in the stratosphere and break down ozone molecules is an imminent reality. A decrease in the concentration of stratospheric ozone would increase the amount of ultraviolet radiation in ambient sunlight. In addition to altering plant and aquatic life in unpredictable ways, increiased ultraviolet radiation will adversely affect human health. The incidence of various types of skin cancers will increase, as will the rate of deaths from skin cancer. In addition, there will be an increase in the occurrence of certain types of ocular cataracts. The most recently described effect of ultraviolet radiation on a biologic system is its ability to alter the immune system in experimental animals and humans. Although much is known about the immunologic effects of ultraviolet radiation, particularly in animal models, little information is available on its potential to decrease host resistance to infectious diseases. This is an important topic that needs to be addressed in order for us to understand fully the consequences of ozone depletion for human health.
Effects of Simultaneous Dietary Exposure to 2,2′,4,4′,5,5′-Hexabromobiphenyl and 3,3′,4,4′,5,5′-Hexachlorobiphenyl on Hepatic Tumor Promotion in Rats
Authors: Evans M. G. , Sleight S. D.
Published: November 2007

Female Sprague-Dawley rats were partially hepatectomized, initiated with diethylnitrosamine (DEN), and fed diets containing 2,2′,4,4′,5,5′-hexabromobiphenyl (245-HBB), 3,3′,4,4′,5,5′-hexachlorobiphenyl (345-HCB), or combinations of 245-HBB and 345-HCB to determine the tumor-promoting ability of these compounds in a two-stage (initiation/promotion) hepatocar-cinogenesis system. Tumor-promoting ability was assessed by measuring hepatic foci positive for gamma glutamyl transpeptidase (GGT) activity. Concentrations of 10 or 100 mg 245-HBB/kg of diet caused significantly increased numbers of GGT-positive hepatic foci. When 245-HBB and 345-HCB were fed simultaneously, an additive effect on tumor-promoting ability was observed at dietary concentrations of 10 mg/kg 245-HBB and 0.1 mg/kg 345-HCB. However, an inhibitory effect on tumor promotion occurred when dietary concentrations of 100 mg/kg 245-HBB and 1.0 mg/kg 345-HCB were fed simultaneously. These results suggest that the tumor-promoting ability of simultaneous exposure to 245-HBB and 345-HCB can be additive or inhibitory depending upon the concentration of each congener in the diet.
Keratinization and Tumor Promotion
Authors: Laskin Jeffrey D.
Published: November 2007

Keratins are the major proteins synthesized by keratinocytes. They consist of a group of 10–20 different polypeptides in the molecular weight range of 48,000–67,000. Keratins associate in cells to form intermediate filaments, the major network of the keratinocyte cytoskeletal architecture. Keratins are produced in cells in a specific, sequential manner during epidermal stratification and the formation of the stratum corneum. Tumor promotion in mouse skin is associated with epidermal hyperplasia and aberrant cellular differentiation. This is accompanied by alterations in normal patterns of keratinization as revealed by high-resolution two-dimensional polyacrylamide gel electrophoresis. Changes in keratinization in mouse skin during tumor promotion may serve as useful markers for the development of neoplasia.
The Role of Free Radicals in Tumor Promotion: Oxy Radical Production by Murine Peritoneal Macrophages In Vivo in Response to Tumor Promoters
Authors: Witz Gisela
Published: November 2007

The studies discussed implicate the production of active states of oxygen-including free radicals in the sequence of events leading to the induction of tumors by promoters. The peritoneal macrophage system can serve as a model system for identifying promoters and antipromoters and can be a tool in studies on the mechanism of tumor promotion.
Neurological Approach to Neurotoxicological Evaluation in Laboratory Animals
Authors: Mattsson Joel L. , Albee R. R. , Eisenbrandt D. L.
Published: November 2007

The neurotoxicological potential of a compound is best evaluated with information from a wide variety of tests. Our philosophy is that tests should be applicable across species and emphasize complementarity to neuropathology. Electrophysiologic tests comparable to those in human clinical neurology fulfill these requirements. Animals are not anesthetized but are physically restrained during the tests. Routine tests include flash evoked potentials, auditory brainstem responses to clicks and tone pips, somatosensory evoked responses, and caudal nerve action potentials. Tests can be added (e.g., H-reflex, EMG, or EEG) or deleted as circumstances warrant. A careful clinical examination of all animals (functional observational battery) and, for rats, a test of grip strength are utilized as well. Neuropathology typically includes perfusion fixation and special stains of histological sections from the central and peripheral nervous systems. Approximately half the animals are retained as a recovery group for subsequent tests if warranted by the results of the neurotoxicological evaluation. The neurological approach, in conjunction with standard toxicological studies, provides data with the necessary breadth and depth for a comprehensive evaluation of neurotoxicity.
Screens in Neurotoxicity: Objectives, Design, and Analysis, with the Functional Observational Battery as a Case Example
Authors: Gad Shayne C.
Published: November 2007

Screening tests for detecting the presence or probable absence of a single end point (such as neurobehavioral activity) are the most common and important activities in toxicology. Objectives and characteristics of screens are presented and reviewed here, and the corresponding essential design features of a neurotoxicology screen are suggested. It is pointed out that such screens should function as the initial phase in some form of multitier process and that they would be most efficiently and effectively performed and accurately interpreted by incorporation into existing study designs. Also presented are the objectives of an analysis of data from screens and the essential relationship of such analysis to those objectives. The types of data encountered are reviewed, along with traditional and alternative approaches to data analysis and their operating characteristics.

Finally, the different current forms of neurotoxicity screens (both primary and secondary) are summarized. The functional observational battery and its history, performance, and limitations are presented in light of the proposed principles as an example case for screening.
Office and Field Diagnosis of Neurotoxic Disease
Authors: Arezzo Joseph C. , Schaumburg Herbert H.
Published: November 2007

Accurate diagnosis of neurotoxic disease requires a fundamental knowledge of the principles of neurology, epidemiology, and toxicology. The cardinal features of the office evaluation of this condition are the detailed history and meticulous clinical examination of an individual; the examination focuses on detecting naturally occurring disease that may account for or mask the principal signs and symptoms. Specialized diagnostic tests can provide an important complement to the office evaluation but are often nonspecific for neurotoxic disease. Field assessment, in contrast, rarely utilizes detailed examinations and depends heavily on quantitative screening tools, such as questionaires, tremor analysis, computer-assisted neurobehavioral tests, and quantitative sensory tests. Field studies generally have two goals: the identification of population cohort differences and the detection of individual members of a group that differ from a population or the expected norm. No single procedure is optimal for all field studies; rather, the methods and analyses should be tailored for the population and toxin under study.
A Toxicologist's Viewpoint of the Quality of Computer-Captured Data and Data Audits
Authors: Siconolfi Richard M.
Published: November 2007

As computers become more common in toxicology laboratories, the need of handwritten data decreases. The good laboratory practice standards taught the toxicology community to prepare adequate standard operating procedures and how to document all phases of a nonclinical laboratory study.

Have computers helped us with our SOPs or documentation? Maybe. Computers have streamlined many of the mundane tasks in data collection. However, they have also opened up a whole list of problems: data security, data audits, computer-generated backups, technician training and periodic updates, system validation (software, hardware, and data), and “data thieves.”

A system of checks and balances must be developed, implemented, and reviewed constantly to assure the quality of data collected. This cannot be the responsibility of one person or one department but requires input from many, the cooperation of all, and support from management, without which quality would suffer.
Sampling Techniques for Data Audits
Authors: Dewoskin Robert S. , Haw John H.
Published: November 2007

The data audit is a critical element in any quality assurance program and an area in which considerably more methods development is needed. To assist the QAU in organizing the requirements of the data audit for bioassay data and in developing a more rational and flexible sampling strategy, a decision tree has been designed. Surprisingly few QA auditors are aware of the many options available in performing a data audit. The general rule of thumb is the 10% audit, but other sampling plans may best represent the potential error rate of the whole data set. Presented here is a step-by-step approach to assist the quality assurance unit (QAU) in organizing the requirements of the data audit for bioassay data and in choosing the best available option. Steps in the development of a sampling plan include (1) defining, identifying, and characterizing data, (2) determining what constitutes an error and how errors are categorized, and, if possible, (3) specifying acceptable error rates.
Quality Assurance: Meeting the Challenge
Authors: Morris Carl R.
Published: November 2007

This presentation outlines the requirements of the study director and the quality assurance unit as defined in the Good Laboratory Practice (GLP) regulations. The qualifications of the quality assurance professional are discussed. The multidisciplinary aspects of quality assurance are stressed.
Developmental Toxicology Evaluation of 1-Pentanol, 1-Hexanol, and 2-Ethyl-1-Hexanol Administered by Inhalation to Rats
Authors: Nelson B. K. , Brightwell W. S. , Khan A. , Krieg E. F. , Hoberman A. M.
Published: November 2007

As part of a large study evaluating the developmental toxicology of industrial alcohols, groups of approximately 15 Sprague-Dawley rats were exposed for 7 h/day on gestation days 1–19 to one of three alcohols at the highest concentrations we could generate as a vapor. Since these concentrations were not sufficiently high to be toxic to the maternal rats, lower levels were not included. These concentrations were 14,000, 3500, and 850 mg/m3 1-pentanol, 1-hexanol, and 2-ethyl-1-hexanol, respectively. Dams were weighed daily for the first week of exposure and weekly thereafter and were sacrificed on day 20. Fetuses were serially removed, blotted dry, examined for external malformations, sexed, weighed, fixed, and examined for visceral or skeletal defects. Pentanol reduced maternal feed intake and weight gain, but there were no significant decreases in fetal weights. Resorptions were slightly increased in the group exposed to 1-hexanol, and 2-ethyl-1-hexanol reduced maternal feed intake, but neither hexanol derivative produced malformations. Obviously, teratogenicity by other routes of exposure cannot be ruled out, particularly in view of the low volatility of these alcohols. However, the present studies indicate that inhalation of pentanol, hexanol, or 2-ethyl-1-hexanol at the stated concentrations can produce limited maternal toxicity, but none was teratogenic to rats.
Quality Assurance Impact: Can It Be Measured?
Authors: Berny Claude , Long David
Published: November 2007

Most quality assurance professionals can rightly claim that their units and the laboratories they inspect work in compliance with good laboratory practice (GLP) regulations. However, compliance itself is only the beginning. Quality assurance (QA) should now turn its attention to the process of optimizing operations in the industry by identifying weak links in the quality chain and working to remove the likelihood of failures and wasted time. Part of this process involves measuring QA impact. Impact can be evaluated in terms of effectiveness or efficiency. The difference between effectiveness and efficiency is discussed here. Measuring effectiveness involves quantifying effects; measuring efficiency involves quantifying the relationship between effect and effort. Some practical approaches to the collection of suitable data are outlined. There are no clear-cut rules for measuring QA impact. So far, the techniques available for assessing impact are rudimentary. However, it is important that all quality assurance professionals tackle the problems of evaluating their impact in order to strive toward higher standards of performance and toward greater understanding of the role of QA within the industry.
An Overview of GLP Implementation in Europe
Authors: Falconi Giovanni , Goeke Jane E. , Morris Carl R.
Published: November 2007

GLP implementation in Europe is complicated by a “diversified” approach. European toxicology testing facilities must be aware not only of their own national regulations but also of the requirements of other European countries as well as several significant non-European nationalities (the United States and Japan). This presentation briefly describes four EEC directives pertaining to GLP implementation in Europe.

These directives provide for (1) performance of audits and inspections by member states; (2) EEC distribution of information regarding GLP compliance; (3) harmonization of inspections and unification of criteria; (4) certification of GLP compliance; and (5) provision of mechanisms to adapt the directives to technical progress.
Developmental Toxicity: Extrapolation Across Species
Authors: Hoar Richard M.
Published: November 2007

There is a pervasive lack of understanding about the definition of a developmental toxicant and the experimental design necessary to differentiate between maternal toxicants and those uniquely, i.e., selectively, hazardous to the conceptus. Thus, the acceptance of the adult-to-developmental (A/D) ratio and its ability to identify those compounds uniquely hazardous to the conceptus has been compromised, as has the extrapolation of hazard across species. The failure to establish a shared understanding is discussed, together with the role of an in vitro screen for determining the A/D ratio. The addition of an environmental exposure factor permitting the extrapolation of hazard assessment across species and the estimation of potential human developmental toxicity is detailed.
Subchronic Toxicity of Sodium Chlorite in the Rat
Authors: Harrington Robert M. , Romano Robert R. , Gates Don , Ridgway Peter
Published: November 2007

Chlorine dioxide (ClO2) is currently used in many countries as a drinking water disinfectant. The chlorite ion (ClO2-) is the primary degradation product of ClO2 when it is used to treat drinking water. In this study, sodium chlorite was administered daily by gavage to rats for 13 weeks at dose levels of 0, 10, 25, or 80 mg/kg/day. At the conclusion of the study, all surviving animals were killed and subjected to a gross necropsy. Hematology, blood chemistry evaluations and urinalysis were performed. At 80 mg/kg/day, there were several treatment-related deaths and morphological changes in erythrocytes were observed. Mean erythrocyte count was decreased in both sexes. In males, hematocrit and hemoglobin levels were decreased and methemoglobin levels were increased. Splenic extramedullary hemopoiesis was observed in some animals at 80 mg/kg/day. At 25 mg/kg/day, methemoglobin was increased in males. No adverse toxicological effects were noted at 10 mg/kg/day.
Evaluation of the Toxicological Risk Associated with the Use of Poly aery lamides in the Recovery of Nutrients from Food Processing Waste (II)
Authors: Schechter LeeAnn , Deskin Randy , Essenfeld Amy , Bernard Bruce , Friedman Marvin , Grube Elizabeth
Published: November 2007

Experiments were conducted using radiolabeled acrylamide and liquid scintillation counting methods to determine how acrylamide monomer would partition during the solid/liquid separation and subsequent rendering of a poultry processing waste. Due to its nutritive value, the rendered solids from such a full-scale food processing waste operation could potentially be used as a component of animal feed. Previous studies were unable to directly measure acrylamide in the solids samples after separation. Based on the analytical data herein, ∼1% of the original radiolabel administered to the waste system was detected in the rendered solids. In a full-scale food processing waste operation, this would represent a maximum level of 0.3 ppb acrylamide in the final animal feed with more typical levels, reflecting industry use, being ∼0.05 ppb. These levels are an order of magnitude less than those calculated in the previous experiment, confirming the associated risk as de minimis.
Tissue-Specific Metabolism of Benzene in Zymbal Gland and Other Solid Tumor Target Tissues in Rats
Authors: Low Lawrence K. , Lambert Charles E. , Meeks J. Ralph , Naro Paul A. , Mackerer Carl R.
Published: November 2007

In vitro studies were carried out to investigate whether target organ susceptibility to benzene-induced solid tumor formation is governed by tissue-specific differences in metabolism. The ability of several target and nontarget tissues to deconjugate and conjugate polar metabolites, to metabolize benzene to phenolic metabolites, to carry out peroxidative biotransformations, and to trap tissue glutathione was evaluated. The Zymbal gland, the organ most sensitive to benzene-induced tumorigenicity, showed extensive phenyl- and aryl-sulfatase activity but no phenol sulfoconjugating activity. Similarly, oral cavity tissue, mammary gland, and bone marrow showed sulfatase activity but lacked sulfotransferase activity. Sulfatase-mediated hydrolysis such as that observed in the Zymbal gland may represent an important pathway by which polar metabolites are shunted from urinary or biliary excretion as their sulfates to delivery to target tissues as phenolic or potentially reactive metabolite(s). Zymbal gland, nasal and oral cavity, and mammary gland tissue homogenates (10,000 g supernatant) all possess oxidative capability to metabolize benzene to phenol, hydroquinone, and catechol. Nasal cavity homogenates produced two-to eightfold higher levels of phenol, hydroquinone, and catechol from benzene than did liver homogenates. Zymbal gland, bone marrow, and oral cavity homogenates, when incubated with hydroquinone and glutathione, produced high levels of 2-(S-glutathionyl)hydroquinone, indirectly indicating the production of 1,4-benzoquinone, a reactive intermediate implicated in benzene toxicity. Peroxidases have been proposed to mediate the oxidation of p-hydroquinone to 1,4-benzoquinone. The Zymbal gland, nasal and oral cavities, mammary gland, and bone marrow all were found to possess greater peroxidase activity than contrasting nontarget tissues did. The metabolic capabilities of target tissues, including the ability to hydrolyze sulfate conjugates to free phenolic compounds, to oxidize benzene to phenolic metabolites, to bioactivate hydroquinone to a reactive intermediate, and to carry out peroxidative reactions may offer possible explanations for the greater susceptibility of these sites to benzene-induced tumorigenicity. Transport of sulfate conjugates and their release via hydrolysis (e.g., through sulfatase action) (“sulfate shunting”) and subsequent oxidation (e.g., through peroxidase action) may represent a novel mechanistic pathway by which potentially reactive benzene metabolites can gain access to target sites and initiate critical genotoxic events.
Intravenous Safety Study in Rats Given Paramagnetic, Polystyrene Beads with Covalently Bound Sheep Anti-Mouse Immunoglobulin G (IgG)
Authors: White R. D. , Glosson J. A. , Gordon D. E. , Northup S. J.
Published: November 2007

The potential for acute toxicity from Dynabeads1 M-450 Sheep Anti-Mouse IgG ST (SAM-Beads) administered once intravenously to male and female rats was assessed. SAM-Beads in saline containing 0.5% plasma protein fraction (PPF) was intravenously administered at dosages of 9.6 times 104 or 8.3 times 108 beads/kg at a rate of ≥2.5 ml/min/kg. Rats administered 9.6 times 104 beads/kg were killed 14 days posttreatment. Rats administered 8.3 times 108 beads/kg were killed either 14 or 42 days posttreatment. Saline containing 0.5% PPF served as the control article. Treatment groups were statistically compared with respect to clinical chemistry, hematology parameters, and body weight data. No significant group differences were detected (α = 0.01) with respect to any statistically analyzed data. No SAM-Beads were detected in urine samples collected overnight posttreatment. No test beads were found in any of the tissues from animals administered 9.6 times 104 beads/kg. The SAM-Beads were evident in the lung, liver, spleen, lymph nodes, kidney, and sternal bone marrow of rats administered 8.3 times 108 beads/kg and killed 14 or 42 days posttreatment. The SAM-Beads observed were recognized as a foreign body and were phagocy-tized by cells of the reticuloendothelial system. The majority of the SAM-Beads were found in the lung, liver, and spleen and were slightly more numerous among animals who were killed at 14 days. There was also a trend toward an increased incidence and/or distribution of phagocytized beads in the bone marrow of animals killed 42 days posttreatment when compared with the 14-day killed animals. A few extracellular beads were present in the lymph nodes, kidneys, and sternal bone marrow. Under the conditions of this study, intravenous administration of Dynabeads M-450 Sheep Anti-Mouse IgG ST did not result in any adverse test-article-related macroscopic, clinical pathologic, or histopathologic changes.
The Synergistic Effect of Feed Restriction and Endotoxemia on Motor Activity
Authors: David Raymond M. , Hosenfeld Ruth S. , Bernard Lisa G. , Vlaovic Milan S. , O'Donoghue John L.
Published: November 2007

The United States Environmental Protection Agency and the Organization for Economic Cooperation and Development have recommended incorporating measurement of motor activity into routine toxicity studies to provide a screen for potential neurotoxic effects. However, there is little information on how to interpretate motor activity levels when an animal's clinical state is altered by systemic toxicity. Because systemic toxicity often includes nonspecific effects, such as reduced feed consumption, this physiologic condition was mimicked by limiting the feed of healthy rats to 10–15 g/rat/day and by limiting appetite through induction of endotoxemia. Injection of animals with endotoxin lowered motor activity by 50%. Combining feed restriction with endotoxin treatment resulted in reduced motor activity 2 days after injection, when signs of endotoxemia were not apparent. Animals treated with endotoxin but fed ad libitum had motor activity levels comparable to the control group 2 days after injection. The results suggest that motor activity levels can be altered by reduced feed consumption in the presence of subclinical systemic toxicity. Significant feed restriction in the absence of systemic toxicity appears unlikely to result in lowered motor activity levels. Key Words: Neurotoxicity-Motor activity-Endotoxin-Systemic toxicity-Feed restriction.
Malachite Green: A Toxicological Review
Authors: Culp Sandra J. , Beland Frederick A.
Published: November 2007

Malachite green, an N-methylated diaminotriphenylmethane dye, is used primarily as a therapeutic agent in aquaculture. In solution, the dye exists as a mixture of the cation (chromatic malachite green) and its carbinol base, with the ratio depending on the pH of the solution; the dye also can undergo chemical and metabolic reduction to a leuco derivative. Analysis offish tissue after exposure to malachite green indicates the presence of both chromatic and leuco forms, with the latter having a much longer tissue half-life. Malachite green intercalates with DNA, with a preference for A:T-rich regions, and the leuco derivative bears a structural resemblance to carcinogenic aromatic amines that can form covalent DNA adducts. Malachite green is mutagenic in Salmonella typhimurium TA98 in the presence of an exogenous metabolizing system. In mammalian cells, it shows marked cytotoxicity and the ability to induce cell transformation and lipid peroxidation. Results from carcinogenicity bioassays with malachite green have been equivocal; however, it appears to act as a tumor promoter, perhaps because of its ability to induce the formation of reactive oxygen species. These characteristics, plus its close structural similarity to carcinogenic triphenylmethane dyes (e.g., gentian violet) suggest that additional data are required to determine if human exposure to malachite green results in adverse health effects.
A Performance Standard for Clinical and Functional Observational Battery Examinations of Rats
Authors: Mattsson Joel L. , Spencer Pamela J. , Albee Ralph R.
Published: November 2007

Clinical examinations are a key component of all toxicology studies and are a major component of the functional observational battery (FOB). The FOB is a core feature of the USEPA neurotoxicity screening guideline of 1991. The need for well-trained technicians is recognized, but technician competency is virtually always judged subjectively by their supervisors. Although subjective evaluation of performance cannot be replaced, what constitutes satisfactory performance is nebulous and therefore difficult to communicate to trainees and difficult to document. Consequently, a laboratory performance standard, with a clear pass-fail criterion, was developed to address this deficiency. The performance standard was an idealized composite of FOB data from experienced laboratory personnel, each person tested on a separate set of four groups of rats. The rats were examined in random order, and treatments were either (a) saline, (b) chlorpromazine, (c) atropine followed by physostigmine, or (d) amphetamine. Thus, the performance standard was the pattern of scores generated by the four treatments. After training, each technician was individually tested on four groups of rats similarly treated (random order, blind examination). The pattern of scores generated by the technician was compared to the performance standard by calculating a Pearson's cross-correlation coefficient. An r > 0.8 was considered passing. The use of the standard meets several laboratory goals: (a) good science (improved training leads to better studies), (b) documentation of observer competency required by the USEPA neurotoxicity guideline, (c) improved documentation of training for Good Laboratory Practices, and (d) objective documentation of performance for purposes of personnel management.
Testicular Response to Exogenous Gonadotropins in Infant Cynomolgus Monkeys
Authors: Sameshima Hidenobu , Hamana Katsumi
Published: November 2007

The response of the testis to exogenous gonadotropins was examined by determining serum testosterone (T) levels and by observing histopathological changes of the testes using 5–7 month-old males. After a single combined injection of 100 IU plus 15 IU human menopausal gonadotropin (hMG) or 500 IU human chorionic gonadotropin (hCG) plus 15 IU hMG, the serum T levels reached peak values 72 h after administration. During repeated aministration of the combined injection of 100 IU hCG plus 15 IU hMG at five 3-day intervals (Day 0, 3, 6, 9, 12), the serum T levels reached peak values 3 days after the first injection, which were about 3 times higher than the mean serum T levels of adult monkeys. The serum T levels decreased gradually on subsequent days of treatment. Three days after the fifth injection (Day 15), the T levels were equal to the T levels of adult monkeys. The testicular volumes on Day 15 were significantly higher than those on the first day of injection. The histopathological examination of the testes (210, 238 mg) obtained from two treated males revealed hyperplasia and hypertrophy of the Leydig cells and spermatogonias, spermatocytes, and mitotic germinal cells were observed in the seminiferous tubule. Only spermatogonia were found in the one testis (150 mg) obtained from an untreated male. From the above results, it was confirmed that the testes of infant cynomolgus monkeys produced T levels in the same way as the testes of adult monkeys in response to the administration of exogenous gonadotropins. Additionally, the initiation of the spermatogenetic process in the testes of infant monkeys was stimulated by exogenous gonadotropins, therefore suggesting that this method could become a useful means to evaluate the testicular function of infant males.
A NORMATIVE STUDY OF AIRFLOW IN CHILDREN
Authors: Beckett Ralph L. , Thoelke William , Cowan Linda
Published: November 2007

Seven‐year‐old youngsters from the University of Missouri at Columbia Laboratory School were subjects for the measurement of vital capacity, phonation air volume, maximum phonation time, and mean flow rate. The children phonated maximally into a respirometer. The group often boys was quite similar in most respects to the group of ten girls. Although certain clear differences were found, they did not achieve high significance with t‐tests. The smaller mean flow rate for the girls is discussed in the light of recent experimental findings.
DOCUMENTATION OF SYNDACTYLY AND TREACHER COLLINS SYNDROME FOR POSSIBLE CONCOMITANT SPEECH DISORDERS
Authors: Massengill Raymond , Willis Viola , Gertner Linda , Fetterolf Judy
Published: November 2007

The speech characteristics of four syndactylyly patients and five Treacher Collins patients are described. Each patient was given a battery of tests including X‐ray analysis, articulation tests, a diadochokinetic rate analysis, to evaluate the speech proficiency and the functioning of the periphreal speech mechanism.

Because of the wide range of associated defects, many involving the speech mechanism, often accompanying these two congenital anomalies, this study does indicate that such cases should be seen and studied by the speech pathologist.
THE ROLE OF AUDIOMETRY IN THE REHABILITATION OF THE LARYNGECTOMIZED PATIENT
Authors: Harrison Robert J.
Published: November 2007

Hearing loss is the most prevalent handicap in the general population and it is a problem that increases in frequency with increase in age. Because most laryngectomized patients are middle‐aged or older males and because of the alteration in the anatomy and physiology during surgery, audiometry can play a vital role in rehabilitation.

The benefits of accurate audiometry are: 1—objective evidence regarding otologic management and its effectiveness; 2—ruling out of hypacusis as a deterrent to esophageal speech progress or mastery of the artificial larynx and 3—utilization of amplification techniques during transient periods of acute middle ear problems. The communicative disorder specialist is the logical professional to conduct this audiometric monitoring but adequate management of the patient involves the close teamwork of the speech pathologist, the audiologist and the otolaryngologist.
A NOTE ON REDUCED AUDITORY PAIN THRESHOLD IN 44 STUTTERING CHILDREN
Authors: MacCulloch Malcolm J. , Eaton Rayleen
Published: November 2007

The threshold of auditory pain has been measured in 44 children referred for stuttering and in 44 control children matched for age and taken from schools in the same geographical area. Pure tone sound was applied via headphones over frequencies from 60 Hz to 300 Hz, across a power range from zero to 250 milli watts. The data consisted of threshold figures at 9 frequencies for 35 boys and 9 girls both in the experimental group and the control group.

Statistical analysis showed that pain threshold in stutterers is lower than for non‐stutters in the groups as a whole, and then when each group is sub‐divided for sex, the females have a lower threshold than do the males. When the results are dichotomised in this way, there is still no overlap between stutterers' and non‐stutterers' threshold.

All the threshold curves have a negative slope with frequency, the thresholds being lowest at 300 Hz.

These data are a new finding, which requires confirmation; they lend weight to those theories of stuttering which state that stuttering has a pathophysiological basis. The possible site of such an abnormality is discussed.
Laryngographic Analysis and Intonation
Authors: ABBERTON EVELYN , FOURCIN A. J.
Published: November 2007

This paper describes the ways in which the output of a device which responds to the vibrations of the vocal folds can be used in speech and language therapy.
Phonological Procedures for Child Language
Authors: CRUTTENDEN ALAN
Published: November 2007

It has often been stated by linguists (e.g. Haas, 1963) that in making phonological analyses of children's speech it must be emphasized that at all stages of development the child has a system of his own and that it is misleading to regard his speech as “an imperfect version of adult language” (Fry, 1968, p. 19). This article suggests that over‐emphasizing such viewpoints, particularly with regard to articulatory disorders, may be as unhelpful as the earlier disregard of functional factors (being “swamped by a mass of observations”) which such emphasis was intended to dispel.
An Experiment in Applying Linguistics to Speech Therapy
Authors: HUTCHISON M. K. F.
Published: November 2007

“This article gives a description of the language behaviour of a group of five children suffering from severe language learning disabilities. The language state prior to, and during, remediation is outlined. This is followed by a more detailed account of the principle teaching techniques used with these children, including a description of some of the anomalies in their language use that have been of concern. The latter half of the article contains a discussion of particular examples where knowledge from linguistics was incorporated into the teaching programme.”
The Use of Psycholinguistic Principles in Treatment of Aphasia
Authors: SEFER JOYCE W. , SHAW ROBERT
Published: November 2007

An understanding of psycholinguistic principles is important for the aphasia therapist. Studies supporting the hypothesis of Chomsky that aphasics have competence but suffer a disruption of performance are cited. The use of some linguistic concepts such as word frequency, linguistic levels, abstractness and association are considered from the point of view of stimulation therapy and indices of recovery.
Variations in Voice Quality with Laryngeal Tumours and Radiotherapy of the Larynx
Authors: ORR N. M. , BSC M. D. HAMILTON , GLENNIE J. McD.
Published: November 2007

Vocal characteristics of a number of patients who had radiotherapy for laryngeal tumours were obtained. It was found that voice quality before treatment was not indicative of the site and stage of the disease. Voice quality after treatment was usually fairly good.

A formula is given for quantitative estimates of hoarseness and is followed by a brief discussion on some of its physical causes.
The Effects of Omissions and Substitutions of Selected Consonants on Intelligibility
Authors: COSTON G. NORMAN , AINSWORTH STANLEY H.
Published: November 2007

Three groups of 10 naive university students were presented taped speech samples (sentences) of the speech of elementary school children. Each sentence contained one articulatory error (omission or substitution) of one of six consonants under study (/r/, /θ/, /z/, /d3/, /s/, and ltñ/). The subjects wrote down what they understood each speaker to say in each of the 72 sentences. Results indicate that in order to compare omissions and substitutions in their effect on intelligibility, each must be qualified by phoneme. Errors on all phonemes do not affect intelligibility to the same degree. The differences between phonemes, however, are not meaningful until qualified by error type. Of the twelve phonemes‐by‐error type studied, /z/ substitutions, /r/ substitutions, and /r/ omissions impeded intelligibility the least. The /θ/ omissions impeded intelligibility more than /z/ and /r/ substitutions and /r/ omissions but significantly less than the other phonemes by error type considered. The /d3/*** substitutions, /θ/ substitutions, /t ñ/ substitutions, /z/ omissions, /s/ substitutions, and /s/ omissions were homogeneous and impaired intelligibility more than the other phonemes‐by‐error type considered.