bluuebunny/crossref_metadata_2025 huggingface dataset:
Some Biochemical and Histological Effects of 2-Chloroethanol in Rats
Authors: Friedman Leonard , Scalera John , Keys James E. , Peters Edmund L. , Gaines Dennis W. , Stone Charles L. , Kasza Louis , Balazs Tibor
Published: November 2007

The effects of 2-chioroethanol (2-CE) on rat tissue following in vitro and in vivo exposure were studied. At concentrations as low as 2.5 mg/ml, protein synthesis in liver slices was inhibited; at concentrations of 25 mg/ml and above, RNA synthesis and respiration were also impaired. Single oral doses of 2-CE to young adult rats at levels of 15-40 mg/kg body weight depressed liver nonprotein sulfhydryl (GSH) concentration and liver protein but not RNA synthesis. Liver lipid was increased by 7 hr after a single oral dose of 30 mg/kg. The time courses and dose-response relationship for GSH depletion and restoration and for protein synthesis inhibition and recovery were similar. The livers of female rats were more sensitive than the livers of male rats to the effects of 2-CE. Protein synthesis was also depressed in kidneys of 2-CE-treated male rats but at higher doses than those needed for this effect to occur in livers of the same animals. Liver polysome disaggregation also occurred after oral 2-CE doses of 20 mg/kg and greater. The effects of 2-CE on ribosome profiles and protein synthesis were at least partially reversed by concurrent intraperitoneal administration of cysteine. The possible relationship of these findings to a role of GSH in protein synthesis is discussed.
Randomization of Animals by Computer Program for Toxicity Studies
Authors: Martin R. A. , Daly A. M. , DiFonzo C. J. , de la Iglesia F. A.
Published: November 2007

Evaluations of the toxic potential of drugs and chemicals often involve statistical comparisons of effects between treatment groups. Such comparisons are valid and permit elucidation of spontaneous versus treatment effects only if the sampling population is obtained without selection bias. Selection bias is routinely minimized or controlled by random sampling or unbiased allocation of animals to treatment groups. A systematic approach using a computerized procedure is described that fulfills these requirements in a simple and efficient fashion.
N,N′-14C-Dinaphthyl-p-Phenylene Diamine Metabolism in the Rhesus Monkey
Authors: Leighty E. G. , Hinderer R. K.
Published: November 2007

The metabolic fate of orally administered 14C-DNPDA containing 0.028% 14C-BNA was studied in the Rhesus monkey, and the aqueous solubility of these 2 chemicals was investigated. Monkeys were given doses of 0,10, or 100 mg/kg 14C-DNPDA via gelatin capsules. Uptake by the blood, tissue distribution, and urine and fecal elimination were monitored for up to 168 hours. In these studies 14C-BNA was 10 to 15 times more soluble than 14C-DNPDA. Very low levels of 14C-DNPDA were observed in the blood, tissues, and urine; most (65–75%) of the parent compound was recovered unchanged in the feces. The blood uptake studies showed that the 14C-BNA impurity is selectively absorbed over the 14C-DNPDA. Although it was not possible to completely rule out the metabolic formation of 14C-BNA, the data suggested that any BNA formed via metabolism is insignificant relative to the contribution of any impurity in the product.
Acute Toxicity of Acrylonitrile: Effect of Diet on Tissue Nonprotein Sulfhydryl Content and Distribution of 1–14C-Acrylonitrile or Its Metabolites
Authors: Jaeger R. J. , Cote I. L. , Rogers A. E. , Silver E. H. , Szabo S.
Published: November 2007

The influence of diet on the acute toxicity (lethality) and distribution of glutathione as measured by tissue nonprotein sulfhydryl (NPSH) concentration following acrylonitrile (ACN) treatment was studied. The tissue distribution of radiolabeled (14C) acrylonitrile or its radioactive metabolites was also determined. The diets tested were a standard laboratory rat chow; a casein-based, complete diet; and 2 diets high in saturated fat content that were either lipotrope deficient or lipotrope supplemented. The latter 2 diets were associated with decreased weight gain in the absence of ACN and increased lethality after orally administratered ACN. The increase in lethality, while most pronounced in the group fed the lipotrope-deficient, high-fat diet, was also seen in rats fed the purified control diet. The high-fat diets were associated with increases in brain and liver NPSH concentrations (mg NPSH/100 g body weight). Following oral administration of 1–14C-ACN, blood contained the highest specific activity. In terms of fraction of administered dose, liver was found to contain the highest total fraction. In the tissues measured, a majority of radioactivity appeared bound to trichloroacetic acid (TCA) insoluble components. The sequence of tissue activity (nCi 14C per g or ml) was as follows: blood > stomach > liver, duodenum, lung, kidney > brain > adrenal. While diet affected toxicity, it did not modify this general ranking.
An Approach to the Design and Analysis of Screening Studies in Toxicology
Authors: Gad S.C.
Published: November 2007

An increasingly important aspect of toxicology is the use of screening tests for detecting the presence or absence of a single end point of effect, such as mutagenicity or neurobehavioral effects. Such screens have a common set of operating characteristics that are not widely apreciated and that make traditional approaches to statistical analysis insensitive and inefficient in comparison to other available methods. All too often, control and historical data are not used to strengthen the analysis process. The characteristics of screens are presented and reviewed, along with overviews of 26 sets of data from functional observational battery screen (neurobehavioral) studies. Two alternative approaches to statistical analysis of screening tests (a control chart approach and a graphic-exploratory data analysis approach) are presented, along with a review of traditionally used contingency table, rank sum, and ANOVA methods. The performances of these methods in analyzing the test case screen datasets are compared in terms of power, sensitivity, and efficiency. Both alternative approaches are shown to be superior to traditional approaches in performance toward meeting the objectives of screens.
Acrylics: A Literature Review of Thermal Decomposition Products and Toxicity
Authors: Johnston P.K. , Doyle E. , Orzel R.A.
Published: November 2007

A comprehensive literature review on the thermal decomposition products and combustion toxicity of acrylics is presented. The types of products produced by the thermal decomposition of acrylic polymers vary widely. At lower temperatures, simple methacrylate polymers are degraded almost entirely to monomer, whereas simple acrylate polymers are degraded primarily to chain fragments and the alcohols corresponding to the ester groups. More complex methacrylate and acrylate polymers appear to be degraded primarily to the olefins corresponding to the ester groups. The major products formed through the thermal decomposition of polyacrylonitrile include HCN, NH3, CO, CO2, and various nitrile compounds. The decomposition of acrylonitrile copolymers (e.g., acrylic and modacrylic fibers) can result in the release of additional compounds. In general, modacrylic combustion products appear to be more acutely toxic than those of other acrylic materials tested or wood. Modacrylic produced a shorter time to incapacitation and time to death than poly(methyl methacrylate) in the FAA test, and, in the NBS test, the LC50 was more than fivefold lower than that for polyacrylonitrile. In addition, the LC50 of modacrylic in the University of Pittsburgh test was an order of magnitude lower than that for the standard test material, Douglas fir.
Phenolics: A Literature Review of Thermal Decomposition Products and Toxicity
Authors: Johnston P.K. , Doyle E. , Orzel R.A.
Published: November 2007

A comprehensive literature review on the thermal decomposition products and combustion toxicity of phenolics is presented. The major decomposition products of phenolics appear to be CO, CO2, H2O, and methane. Smaller quantities of H2, formaldehyde, and other volatile organics, including phenol, methylphenols, and dimethylphenols, also appear to be produced. The types and quantities of thermal decomposition products and the temperatures at which they are produced depend on numerous factors, including the resin structure and formulation and the conditions of degradation. Phenolics produced products that were indicated to be more acutely toxic than other cellular plastics tested by one researcher and were described as “more toxic than wood” by another researcher. Carbon monoxide appears to be the major toxicant produced by the combustion of phenolics. Sensory irritation as indicated by reduced respiratory rate may be due to formaldehyde production; however, sensory irritation is lower than that produced by wood.
A Statistical Approach to the Construction and Analysis of Isobolograms
Authors: Carter Walter H. , Gennings Chris , Staniswalis Joan G. , Campbell Eleanor D. , White Kimber L.
Published: November 2007

Current statistical procedures used in the construction of isobolograms do not use recent advances in mathematical statistics. The variability in the experimental data is either ignored or incompletely accounted for in the analyses. The decision procedures currently used to characterize the type of interaction between two agents do not permit the determination of the level of statistical significance associated with a given conclusion. Furthermore, the often formidable sample size is not exploited in the current isobologram methodology. Statistical techniques exist that may be used to construct isobolograms and decision procedures with a reliable level of significance. An isobologram is a contour of constant response of the underlying dose-response surface. Consequently, response surface methods (RSM) are useful in the estimation and analysis of isobolograms. The interaction between ethanol and chloral hydrate in female ICR mice was evaluated using the RSM approach by fitting the logistic model to quantal data. The loss of righting reflex was quantitated in mice 30 min after coadministration of the two drugs, injected IP on a body weight basis (mg/kg). The study consisted of 39 groups with 6 animals per group. Analysis of our data supports the conclusion of synergy between the drugs as reported by others; however, our results were obtained with a significantly smaller number of animals. These studies also demonstrate that response surface modeling can be used for determining additivity, synergism, and antagonism at a given preselected level of significance.
Assessing Physostigmine Efficacy by Response Surface Modeling: A Comparison to Pyridostigmine Efficacy
Authors: Gennings C. , Carchman R. A. , Carter W. H. , Campbell E. D. , Boyle R. M. , Staniswalis J. G. , Jones D. E. , Reid F. M. , Koplovitz I.
Published: November 2007

The therapeutic efficacy of atropine sulfate/pralidoxime chloride (ATR/2-PAM) treatment therapy and physostigmine (PHY) pretreatment therapy was evaluated in soman-challenged guinea pigs. Response surface analysis (RSM) of treatment efficacy indicated that the optimal ATR/2-PAM dose combination varied as a function of both the soman (GD) challenge level and the PHY pretreatment dose. Efficacy was, therefore, evaluated for varying PHY pretreatment doses in combination with the appropriate optimal ATR/2-PAM treatment (as determined by RSM for each soman challenge dose and PHY dose evaluated). The response surfaces depicting the effects (i.e., probability of survival) of ATR/2-PAM combinations at fixed levels of PHY and GD are presented, and confidence regions and point estimates for optimal ATR/2-PAM treatment combination are included. It was estimated that with optimal therapy a protective ratio (PR) of 6 can be observed. Comparisons were made between the use of PHY/ATR/2-PAM as presented here and the use of PYR/ATR/2-PAM, as discussed by Jones et al.(1) Both studies showed a strong positive (r ≥ 0.98) relationship between dose and the PR. However, the estimated slope parameter for PHY was significantly larger ( P < 0.001) than the slope parameter for pyridostigmine (PYR). This difference in slopes may indicate different mechanisms of action for PYR and PHY.
Analysis of Uncertainty and Reaching Broad Conclusions
Authors: North D.W.
Published: November 2007

Probability theory can provide a general way of reasoning about uncertainty, even when data are sparse or absent. The idea that probabilities can represent judgment is a basic principle for decision analysis and for the Bayesian school of statistics. The use of judgmental probabilities and Bayesian statistical methods for the analysis of toxicological data appears to be promising in reaching broad conclusions for policy and for research planning. Illustrative examples are given using quantal dose-response data from carcinogenicity bioassays for two chemicals, perchloroethylene and alachlor.
Screening Approaches to Neurotoxicity: A Functional Observational Battery
Authors: Moser Virginia Clayton
Published: November 2007

Observational tests to assess the behavioral and neurologic integrity of laboratory rats have been advanced for use in the primary screening of chemicals to detect neurotoxic potential. To examine the use of such an approach, we are systematically using a functional observational battery (FOB) to characterize known neurotoxicants and to assess its selectivity, reliability, specificity, and sensitivity. Our FOB is a series of tests that includes home cage and open field observations, neuromuscular and sensorimotor tests, and physiologic measures. Described in this article are the compounds we have tested to date and how the data have been integrated to produce a profile of effects for each. We have found the FOB to be sensitive to a variety of neurotoxicants, whose effects can be distinguished using a type of profile analysis as illustrated herein. This research effort provides important information about both the execution and the interpretation of FOB studies.
Nonhuman Primates in Neurotoxicity Screening and Neurobehavioral Toxicity Studies
Authors: O'Keeffe Robert T. , Lifshitz Kenneth
Published: November 2007

Nonhuman primates can be used to develop models that use complex behaviors to evaluate the toxicity of pharmaceutical and other products, Primate functional observational batteries (FOBs) can be designed to resemble those used in rodent tests, although they need not focus on simple conditioned motor responses as small mammal FOBs frequently do. Primates generally are not suitable for use in most (first-tier) neurotoxic screening tests for both practical and scientific reasons, as well as for ethical ones. With regard to practicality factors of cost, animal availability, husbandry, and housing, and observer labor intensity, all increase with the use of primates. With regard to research design, accumulating evidence indicates that primate pharmacologic responsivity is affected by social variables in such a way that group-housed animals provide more realistic (valid) models of human neurobehavioral and disease processes in general. This further complicates primate use and behavioral measurement and evaluation. Data from a long-term study of semipermanant behavioral and electrophysiologic alterations brought about by extended exposure to a psychoactive medication are presented in order to illustrate these points and to indicate how such measures can be useful, and at times indispensable, in second-tier evaluation.
Data Evaluation and Statistical Analysis of Functional Observational Battery Data Using a Linear Models Approach
Authors: Creason John P.
Published: November 2007

Statistical analysis of functional observational battery (FOB) data presents special problems in that there are three different types of data collected (continuous, count, and categorical), all of which are measured in a repeated manner across time. Initial measurements are made before any treatment is applied, and proper use of these individual control values must be determined. A coherent structure for the analysis of such data is laid out, and examples of applications are presented. Rationale for the approaches used are described. Behavioral characteristics of the statistical tests are summarized for one FOB experiment to show that the tests indeed perform properly. The availability and ease of use of the SAS statistical software employed, including the key analysis procedures PROC CATMOD and PROC GLM, and of the SASGRAPH graphics procedures and their importance to data evaluation in the FOB are fully described. Cautions about these procedures and further statistical research and development needs are summarized.
Learning and Memory: Considerations for Toxicology
Authors: Peele David B.
Published: November 2007

The goal of this article is to outline a strategy for assessing chemical-induced dysfunction of learning and memory in laboratory animals. Toward that end, several questions are raised, including if tests of learning and memory should be included in a primary screening effort, what considerations should guide the selection of particular test methods, and experimental designs. Examples are provided demonstrating that tests of learning and memory can be simple and cost-effective, yet still provide meaningful data on the specificity of effects and on the neural mechanisms involved in chemically induced neurotoxicity.
Chromium(VI) Toxicity: Uptake, Reduction, and DNA Damage
Authors: Standeven Andrew M. , Wetterhahn Karen E.
Published: November 2007

Much recent data supports the “uptake-reduction” model explaining the carcinogenicity of chromium(VI) compounds and the lack of carcinogenicity of chromium(III) com pounds. Cr(VI) readily enters cells by diffusion through a nonspecific anion channel, whereas cells are relatively impermeable to Cr(III). Glutathione appears to facilitate Cr(VI) uptake by reducing Cr(VI) to Cr(III) after it enters the cell, presumably keeping intracellular Cr(VI) concentration low and allowing for further Cr(VI) uptake. Some other nonenzymatic factors, for example, ascorbate and riboflavin, as well as enzymes, such as cytochrome P-450, DT-diaphorase, and the mitochondrial electron transport chain complexes, are capable of reducing Cr(VI) in vitro, but their contribution in vivo is not clear. Cr(VI), once reduced intracellularly, produces various forms of DNA damage including DNA interstrand crosslinks, DNA-protein crosslinks, DNA strand breaks, and Cr-DNA adducts. The pathway of Cr(VI) metabolism in different tissues appears to influence the type of “reactive intermediates” produced, for example, Cr(V) and radical species, and thus the nature and extent of DNA damage. This DNA damage presumably accounts for observed functional changes in DNA replication and transcription which may be crucial to the carcinogenicity of chromium(VI) compounds.
Evaluation of the Miniature Swine for Use in Immunotoxicity Assessment: I. Quantitation of Humoral Responses to Sheep Red Blood Cells and Effects of Cyclophosphamide
Authors: Hinton Dennis M. , Khan Mushtaq A.
Published: November 2007

T-cell-dependent and t-independent humoral responses as well as cell-mediated re-sponses(1) were assessed with groups of young, Hormel-Hanford miniature swine. Test antigens established in various immunotoxicity studies with rodents were used. Results with the widely used t-dependent test antigen, sheep red blood cells (SRBC), are presented in this report. Groups of swine were immunized with varying dosages of SRBC to evaluate basal responses. Serum antibody titers were estimated by the standardized hemolysin (HLY) visual endpoint (EP) assay and a quantitative spectro-photometric (SP) variation using highly purified immunoglobulin (Ig) M and Ig G standards. The sensitivity of the EP HLY assay is about 0.5-1.0 μg for Ig G anti-SRBC; the SP variation is 10 times more sensitive. Peak responses were obtained 7 days after either the first or second injection for both males and females. Peak responses for females, however, were two to four times greater than those in males. Ig M antibodies had a three times higher specific HLY titer than those in the Ig G class. Use of purified antibody standards in either assay variation permitted conversion of dilution titers to specific amounts of antibody. The latter is a more meaningful parameter for various comparisons in either inter-or intraspecies evaluations in immunotoxicity studies.

To evaluate SRBC as a test antigen, low and intermediate doses of the immunotoxicant, cyclophosphamide, were given i.p. starting 2 days before SRBC injection. Antibody levels were reduced correspondingly to approximately 25 and 60% immunosuppression for the two dose levels in both primary and secondary responses. After 2 weeks of rest, animals recovered from treatment with CP. These studies demonstrate that SRBC immunization can be used in the FDA, Hormel-Hanford miniature swine to evaluate the immunotoxicity potential of chemicals without adjuvants or apparent harmful effects to the animal.
Flexible Polyurethane Foam: A Literature Review of Thermal Decomposition Products and Toxicity
Authors: Orzel R. A. , Womble S. E. , Ahmed F. , Brasted H. S.
Published: November 2007

This report presents a comprehensive literature review of the toxicity of the combustion products of flexible polyurethane foam and the thermal decomposition products of this polymer.

Combustion toxicity results obtained using different test methods but measuring the same toxicologic endpoints were compared. That is, time to incapacitation and time to death using the USF and FAA test methods were compared. Also, LC50 values using the DIN, NBS, and University of Pittsburgh tests were compared. The results indicate that despite the use of different test methods, foam densities, formulations, fire retardants, and other additives, combustion toxicity data were generally considered comparable when similar endpoints were compared. Neither CO nor HCN appeared to be the primary cause of death due to the combustion products of flexible polyurethane foam, although they were probably contributory factors.

Under conditions of oxidation and pyrolysis, polyurethane foams decomposed into a liquid polyol component and a “yellow smoke.” The polyol decomposed into CO, CO2, and low-molecular-weight hydrocarbons including ketones, ethers, and/or esters. At high temperatures (greater than 800°C), the “yellow smoke” decomposed into HCN and other nitrogen-containing compounds such as acetonitrile, acrylonitrile, and benzonitrile. Twice as much HCN was produced under pyrolytic conditions as in oxygen-rich atmospheres. Various amounts and types of other combustion compounds were produced, depending on the temperature and oxygen availability.
Practical Application of Microcapsulation for Toxicity Studies Using Bromodichloromethane as a Model Compound
Authors: Aida Y. , Ando M. , Takada K. , Momma J , Yoshimoto H. , Nakaji Y. , Kurokawa Y. , Tobe M.
Published: November 2007

Gelatin-starch syrup (food grade) microcapsulation was applied for toxicology studies of bromodichloromethane (BDCM). BDCM concentrations were stable for 120 days in the microcapsules and for 9 months when incorporated in the powder diet. BDCM concentration in the blood following the administration of microcapsules in olive oil suspension was retained at higher levels than when BDCM was administered as olive oil solution. Subsequently, the microcapsules were mixed in powder diet and were given at concentrations of microcapsulated BDCM of 0, 0.024, 0.072, and 0.215% to groups of 7 male Wistar rats for 1 month. For comparison, BDCM dissolved in olive oil was administered by gavage to groups of 7 male rats for 1 month at dosage levels adjusted to those in the feeding study (0, 20, 60, and 180 mg/kg body weight). Suppression of body weight gain was seen in the high-dosage groups in both the feeding and the gavage studies and was more severe in the former. Similar histopathologic lesions in the liver were shown in both studies, including vacuolization, swelling, and single necrosis of liver cells. Hepatic cord irregularity and bile duct proliferation were observed in the feeding study but not the gavage study. Serum biochemical changes, such as decreases in glucose, triglyceride, and cholinesterase levels, which reflected the histopathologic findings in the liver, were also observed in both studies. Accordingly, the microcapsulation process was proved to pose no qualitative toxic effects on toxicity of BDCM in short-term toxicity studies. It is concluded that the application of microcapsulation is useful for toxicity tests of volatile chemicals when incorporated into food.
Quantitative Neurobehavioral Testing in Humans for Assessing Potential Effects of Occupational Exposure
Authors: Letz Richard
Published: November 2007

Neurobehavioral tests have proven useful as noninvasive indicators of subtle neurotoxic damage. We have developed a computer-administered neurobehavioral testing system for application in a wide variety of situations for evaluating the neurotoxic effects of toxic substances in humans. Performance on these tests has been reported to be impaired by controlled laboratory exposure to known neurotoxic substances. In addition, epidemiological studies have been conducted that show poorer performance on these tests associated with subacute and chronic exposure to neurotoxicants encountered in the workplace. A number of laboratories are currently using this system. Additional work on the most appropriate methods of data analysis is necessary, but a data base collected with a standard instrument will facilitate such efforts. An argument for behavioral surveillance as a part of routine medical monitoring in industry is presented.
Short-Term Toxicity (1 and 10 Days) of Cadmium Chloride in Male and Female Rats: Gavage and Drinking Water
Authors: Borzelleca Joseph F. , Clarke Elizabeth C. , Condie L. W.
Published: November 2007

Male and female Sprague-Dawley-derived rats received CdCl2 by gavage at doses of 25, 51, 107, and 225 mg CdCl2 per kg body weight per day for 1 or 10 consecutive days or in drinking solutions at concentrations of 13–323 mg CdCl2 per liter for 10 consecutive days. There were appropriate controls. In the 1 day study in males only, an apparent treatment-related but not statistically significant decrease in body weight was reported; spleen weights and ratios were significantly lower and lung weights and ratios were significantly higher (in the highest dose only). Dose-dependent mortality was observed in the 10 day gavage study. Body weight gain was depressed in a dose-dependent manner in both males and females. Weights and/or ratios of brain, liver, spleen, lungs, thymus, kidneys, and testes of treated males were depressed in a dose-dependent manner. In females, weights and/or ratios of liver, spleen, thymus, and kidneys were depressed in a dose-dependent manner. Focal necrotic changes in renal tubular epithelium and tubular degeneration were reported in males and females. Testicular and hepatic histopathologic changes (testicular atrophy and necrosis and hepatic necrosis) were also reported in males. In the drinking water study, males demonstrated dose-dependent decreases in body weight gain and weight and/or ratios of liver, spleen, thymus, and kidneys. There were no significant compound-related effects in females, although liver weights and ratios were lower. There were no compound-related histopathologic effects.
Marketed Human Pharmaceuticals Reported to be Tumorigenic in Rodents
Authors: Davies Thomas S. , Monro Alastair
Published: November 2007

The 1994 U.S. Physicians' Desk Reference reports the results of rodent carcinogenicity tests on 241 pharmaceutical agents. Positive results were reported for 101 agents, with a class label implying a carcinogenic hazard also attached to 9 estrogenic, 4 androgenic, and 3 progestogenic agents. Of the positive agents tested in both rats and mice, 39 of 72 were positive in both species, 22 were positive in rats only, and 11 were positive in mice only. There were few (19) unequivocally genotoxic agents, and only one of these was not reported to be tumorigenic to rodents. The liver was a common target organ in rats and mice. In rats, the other most common target organs for tumors were (in decreasing order) the thyroid, testis, mammary, adrenal, and pituitary. In mice, the only other common target organ was the lung.
A Collaborative Study in Japan on Optimal Treatment Period and Parameters for Detection of Male Fertility Disorders Induced by Drugs in Rats
Authors: Takayama Satoshi , Akaike Masashi , Kawashima Kunio , Takahashi Michihito , Kurokawa Yuji
Published: November 2007

The tripartite-harmonized International Conference on Harmonization reproductive guideline (1993) recommends administration of test substances for 4 weeks to male rats before mating. However, scientific or experimental rationale for this recommendation is not firmly based, and the most appropriate parameters have not been established in experimental models. Therefore, a team consisting of 16 Japanese pharmaceutical companies and the National Institute of Health Sciences performed a collaborative study to determine the optimal period and parameters for detection of male fertility disorders in rats. Sixteen compounds, including four anticancer drugs, two psychotropic drugs, two nootropic drugs, two vitamins, two hormones, one antihypertensive agent, one diuretic drug, and two general chemicals were administered to male rats for 4 or 9 weeks before mating. Parameters used to examine effects on the male reproductive system were organ weights, sper-matogenic endpoints, mating behavior, cesarean section findings, and histopathology. From the results, treatment for 4 weeks before mating was concluded to be sufficient to detect adverse effects on male fertility, with the histopathology of the testis being the most sensitive index for the drugs used. Sperm parameters, especially number, and genital organ weight determination provided information confirming toxicity. Tests of reproductive activity were generally found to be insensitive, except where the drugs affected sperm maturation. Based on this study, it is concluded that a 4-week treatment period is appropriate for detection of drug effects on male fertility, and that histopath-ological examination of the testis is the most sensitive approach.
Soaps and Detergents: Alternatives to Animal Eye Irritation Tests
Authors: Christian Mildred S. , Diener Robert M.
Published: November 2007

An extensive computer search was conducted, and a comprehensive overview of the current status of alternatives to animal eye irritation tests was obtained. A search of Medline and Toxline databases (1988 to present) was supplemented with references from sources regarding in vitro eye irritation. Particular attention was paid to soap and detergent products and related ingredients. Eighty-five references are included in the review; the in vitro assays are categorized, and their predictive values for assessing acute ocular irritation are evaluated and compared with the Draize rabbit eye irritation assay and with each other. The present review shows that the increased activity of scientists from academia, industry, and regulatory agencies has resulted in substantial progress in developing alternative in vitro procedures and that a number of large, interlaboratory evaluations and international workshops have assisted in the selection process. However, none of these methodologies has obtained acceptance for regulatory classification purposes. Conclusions drawn from this review include that (a) no single in vitro assay is considered capable of replacing the Draize eye irritation test; (b) the chorioallantoic membrane vascular assay (CAMVA) or the hen egg test-chorio-allantoic membrane test (HET-CAM), the chicken or bovine enucleated eye test, the neutral red and plasminogen activation assays for cytotoxicity, and the silicon microphysiometer appear to have the greatest potential as screening tools for eye irritation; and (c) choosing a specific assay or series of assays will depend on the type of agent tested and the impact of false-negative or false-positive results. New assays will continue to be developed and should be included in future evaluations, when sufficient data are available.
Trade Problems Arising from Differing Maximum Residue Levels for Veterinary Drug and Pesticide Residues
Authors: Carnevale Richard A.
Published: November 2007

An international effort is under way to harmonize the procedures and assumptions used for establishing maximum residue levels (MRL) for residues of veterinary drugs and pesticides. Apparent conflicts in MRLs may not actually reflect differing safety assessments for the residues but may be due to different safety factors, methods of analysis, consumption factors, etc. Equivalence is an important principle in the U.S. position on agricultural trade. Countries wishing to export food products to the U.S. must demonstrate that their country's residue control programs are equivalent to the U.S. program. From the U.S. export perspective, there have been several instances of trade problems resulting from different MRLs. The most significant was the decision by the European Economic Community not to accept U.S. beef if the animals were administered anabolic steroids. Another example involved the Japanese rejection of U.S. pork because of sulfamethazine residues. These examples illustrate the importance of harmonization to future efforts to facilitate free trade and reduce the resource burden on government regulatory bodies.
Use of Dietary Exposure Estimates for Harmonization
Authors: Fitzpatrick Suzanne C.
Published: November 2007

Trade problems arise when different maximum residue levels (MRLs) are established for the same compound. This is often interpreted as a difference in the safety evaluation of the residues of the drug. These differences may also result from different agricultural or veterinary practices, different analytes in the monitoring program, or other factors unrelated to the safety assessment. Thus, an important question for deciding the acceptability of an MRL should be whether use of the MRL will result in residues above a country's established acceptable daily intake (ADI). The ADI, rather than the MRL, is the safety standard for the compound because is defined as the amount of residue that can be ingested daily over a consumer's lifetime without appreciable health risk. It is possible to predict whether there is a realistic possibility that uses of a particular MRL will result in a dietary intake that exceeds the ADI. MRLs should be considered “equivalent” for purposes of trade and consumer safety if use of the MRL does not result in residues above a country's ADI.
A Case Study: Harmonization of Veterinary Drug Maximum Residue Levels Between the U.S. and Canada
Authors: Brynes Steven D. , Teske Richard H.
Published: November 2007

The Free Trade Agreement between the United States and Canada (FTA) went into effect January 1, 1989. To implement certain provisions of the agreement on technical regulations and standards, the United States Center for Veterinary Medicine, the Canadian Bureau of Veterinary Drugs, and Agriculture Canada established the Working Group on Veterinary Drug Tolerances. The primary charges to the Working Group on Veterinary Drug Tolerances were (1) to harmonize the procedures used for evaluating new animal drugs, performing risk assessments and calculating tolerances, and (2) to harmonize the tolerances (or maximum residue levels, MRLs) for approved drugs, with the goal of having the same tolerances in each country. The first of these charges was met early in the negotiations. Both the US and Canada will use a 6-step evaluation procedure for the human food safety evaluation of new animal drugs. On September 29, 1990, Canada published a list of MRLs for 38 drugs that had been harmonized through the FTA. The progress of the working group and its continuing efforts to harmonize tolerances for approximately 15 other veterinary drugs will be discussed. This paper proposes use of the toxicologically determined acceptable daily intake (ADI) for the drug as the safety standard for reaching conclusions on the acceptability of residues in meat for human consumption. Specifically, the ‘equivalence’ of different MRLs for the same veterinary drug would be determined by considering whether they are likely to result in dietary residues that exceed the other country's ADI for the drug. Estimates are made for the veterinary drugs lasalocid and halofuginone hydrobromide. Based on these estimates, the US and Canadian MRLs for each drug would be considered ‘equivalent’ for trade purposes.
VOICE QUALITY AND INDEXICAL INFORMATION
Authors: Laver John D. M.
Published: November 2007

The outline of a componential descriptive model of voice quality is suggested, in the hope of facilitating discussion about voice quality among phoneticians, linguists, speech therapists, psychologists and psychiatrists. Emphasis is laid on the function of voice quality as an index to biological, psychological and social characteristics of the speaker.
SPEECH THERAPY MANAGEMENT FOLLOWING LARYNGECTOMY
Authors: Gordon Margaret T.
Published: November 2007

Proficient alaryngeal speech can be acquired by 76% of patients if adequate speech therapy is given following operation. Patients should be taught to introduce air into the oesophagus by injection aided by lower costal diaphragmatic breathing. Speech therapy should be begun immediately the patient is informed that laryngectomy is necessary and, in the absence of other complicating factors, should be continued intensively in some form until he has acquired useful speech and has returned to full employment, if under retiral age. An artificial larynx should be provided only in the case of a patient who is unable to acquire a competent oesophageal voice.
A COMPARATIVE STUDY OF METHODS FOR TEACHING POST‐LARYNGECTOMY SPEECH
Authors: Simmons Mary Frances , Shanks Susan Jane , Austin Stephen F. , Fresno
Published: November 2007

The authors have compared the therapeutic constructs of six authorities in alaryngeal speech. Three major and one minor type of post‐laryngectomy speech are described, methods of air intake are reviewed, and therapy procedures are contrasted. Reasons for using an artificial larynx are given. An approach which meets the needs of the person is recommended.
FEATURES OF A PSYCHOLOGICAL AND PHYSIOLOGICAL STUDY OF ARTICULATORY PERFORMANCE
Authors: Fawcus R.
Published: November 2007

This article is a description of the preliminary stages of a study of articulatory behaviour. An attempt is made to show how improvement in physical and physiological techniques in both research and treatment requires a similar level of development in the application of psychological principles.

No attempt has been made at this stage to relate performance to linguistic criteria above the phonological level. Such a step is obviously as important as either psychological or physiological analyses.
CHILDREN'S IDENTIFICATION AND DISCRIMINATION OF PHONEMES1
Authors: Locke John L. , Goldstein Jeffrey I.
Published: November 2007

Two experiments are reported in which children's phoneme perception was assessed and studied in relation to their production of phonemes. In the first experiment, 23 kindergarten Ss attempted to identify the correct and incorrect forms of phonemes they articulated correctly or incorrectly. In the second experiment, 56 kindergarten Ss were asked to identify, as in Experiment I, but also they attempted to discriminate between the same sounds in minimally different pairs. Analysis revealed a mild relationship between children's production and perception of specific phonemic contexts and showed the identification task to be slightly more sensitive in detecting children's misperceptions of phonemes they misarticulated.
INFANTILE AUTISM: SOME COMMENTS ON ASPECTS OF DIFFERENTIAL DIAGNOSIS
Authors: Ives L. A.
Published: November 2007

The history of a boy aged 7 years 5 months, presenting as a true example of infantile autism, is given.

The employment of the term “autistic” to describe:

abnormal behaviour in severely subnormal children;

stress reactions in children with developmental language disorders or minimal cerebral dysfunction affecting language and non‐verbal skills; or

children with defective personality development; when these children do not satisfy the criteria for infantile autism, is discussed. The possibility of confusion when “autistic”, as used to describe these children, could be thought by some workers to be synonymous with infantile autism, is stressed.

An observation sheet which the present writer finds useful for recording affect in infants and children seen in the Department of Audiology and Education of the Deaf, Manchester University, is described and discussed with reference to children in the categories mentioned above in Section II.

Problems of psychogenic aetiology, the wide scatter in developed intelligence in children with infantile autism, and educational diagnosis and placement are discussed.
RATIONALE AND SHORT DESCRIPTION OF THE QUEENSLAND UNIVERSITY APHASIA TEST (Q.U.A.T.)*
Authors: Tyrer J. H. , Jordan J. M.
Published: November 2007

Advantages are described of having a battery of comprehensive Language Performance Tests, with Parallel Forms, to measure reliably and repeatedly over a 2–3 year period the linguistic defect in adult aphasia. The requirements for such an aphasia test are discussed and a short description is given of the Queensland University Aphasia Test (Q.U.A.T.). This Test comprises language performance tests on four channels of communication: Auditory Comprehension (A.C.), Oral Expression (O.E.), Reading (R.) and Writing (W.). Each of these channels is divided into 4–11 Sub‐tests, which in turn are mostly divided into 2–10 Items of (predicted) graded difficulty; each Item is divided into 8–12 Sub‐items of (predicted) equal difficulty. These predictions are currently being tested on a randomly selected population of pre‐school and school children. From the Sub‐items attempts will be made to construct 3 or 4 Parallel Forms of the Q.U.A.T.

The fact that the Q.U.A.T. is being standardized on children aged 2–14 years does not mean any commitment to the view that language loss or impairment in aphasia is necessarily a reversion to the stages of language development in children.
The case of Linguistics: A prognosis
Authors: CRYSTAL DAVID
Published: November 2007

This paper presents a discussion of the role of linguistics in relation to the study and treatment of linguistic disorders. An empirical, a methodological, and a theoretical contribution are distinguished, and illustrated from recent research. Particular attention is paid to the complexity of sociolinguistic and psycholinguistic factors affecting language study, to the development of fresh techniques of analysis, and to the need to be aware of the kind of problems which impede the analysis and description of language structures and functions. There follows a review of the main limitations of linguistics in its relationship with speech therapy; and the paper concludes with a brief summary of the present state of the art from the viewpoint of the goals outlined at the beginning of the discussion. The main theme is that the primary relevance of linguistics is as an aid in the development of a more explicitly principled therapy.
The Role of Babbling in the Child's Acquisition of Language
Authors: REES NORMA S.
Published: November 2007

The nature of babbling and its function(s) in the development of language in children are viewed differently by each of two major theoretical approaches. The learning theory approach accounts for babbling in the development of phonological skills, but not for normal variation in babbling behaviour or the relationship between babbling and other aspects of language development. The maturational approach postulates no significant relationship between babbling and the normal development of language. The resolution of these viewpoints must await further normative data on the limits of normal babbling behaviour.
A Directional Change in Tongue Thrust
Authors: WEISS CURTIS E.
Published: November 2007

During the past decade the number of different remedial procedures in tongue thrust have proliferated greatly. The need to improve differential diagnosis, to validate, not necessarily increase, the myriad of treatment and its effectiveness, and to share successful techniques is becoming more apparent. Several questions are raised relevant to the actual existence of the “tongue thrust syndrome”.
An Experiment in Manual Communication
Authors: FENN GILLIAN , ROWE JACQUELINE A.
Published: November 2007

An attempt to develop language through the medium of manual signs in a group of children with multiple handicaps is reported. The language programme based on a “telegraphic” approach is described, and an analysis of progress in both comprehension and expression is presented.
The Phonological Analysis of Articulation Disorders*
Authors: GRUNWELL PAMELA
Published: November 2007

The paper presents a short review of the ideas and aims of previous linguistic studies of articulation disorders. The traditional, now unsatisfactory, definition of “dyslalia” is critically evaluated, and an approach is made to a “typology” of severe articulation disorders. Several analytical techniques are suggested and exemplified, which demonstrate in a simple form the linguistic nature of the disorder, from both the phonetic and phonological points of view, and which provide guidelines in planning remediation. The implications of such disorders for a psycholinguistic model are discussed in the light of the child's apparent ability to comprehend normal spoken English.
Stuttering as “False Alarm” Responding
Authors: SHERRARD CAROL A.
Published: November 2007

It is hypothesised that a stutter is a false alarm, or superfluous correction response to speech feedback signals, such that the overt behavioural response is the repetition of a speech unit. The experiment attempts to elicit stuttering in normals by setting up two conditions, anxiety and divided attention, in which false alarms in any perceptual‐motor task would be predicted. The divided attention condition does increase stutters. The anxiety condition does not increase stutters, but increases the probability of a speech error being corrected, indicating that anxiety directs attention to speech feedback. Auditory masking reduces stutters in all conditions, demonstrating the crucial role of auditory feedback in normal as well as in pathological speech disfluencies. The distribution of elicited stutters is analogous to the distribution of false alarms in orthodox signal detection experiments.
Intersensory Processing Efficiency of Fluent Speakers and Stutterers
Authors: COHEN MELVIN S. , HANSON MARVIN L.
Published: November 2007

Inefficient performance on auditory‐visual tests of intersensory integration is thought to be a sensitive indicator of certain specific types of cerebral dysfunction which cannot be detected by standard neurological examination. The present study was designed to assess the proficiency of fluent speakers and stutterers at matching auditory‐temporal (tapping) patterns with visual‐spatial (dot) displays. A modification of the Birch and Belmont test of auditory‐visual integration was administered to twenty pairs of matched stutterers and fluent speakers. Results indicated that the stutterers' performance on this particular intersensory integration task was significantly lower than that of their fluent peers. This finding was interpreted as supporting the theory that the cortical organisation of stutterers might somehow be different from and less efficient than that of fluent speakers. Stutterers would seem to possess some type of specific neurological dysfunction which prevents or interferes with their ability to perform efficiently in receptive functions such as intersensory integration as well as in the expressive skill of fluent speech production.