Experimental Pathology Laboratories Inc.
Experimental Pathology Laboratories Inc.
Delorme M.P.,DuPont Company |
Muro Y.,Showa Denko K.K. |
Arai T.,Showa Denko K.K. |
Banas D.A.,Experimental Pathology Laboratories Inc. |
And 3 more authors.
Toxicological Sciences | Year: 2012
A subchronic inhalation toxicity study of inhaled vapor grown carbon nanofibers (CNF) (VGCF-H) was conducted in male and female Sprague Dawley rats. The CNF test sample was composed of > 99.5% carbon with virtually no catalyst metals; Brunauer, Emmett, and Teller (BET) surface area measurements of 13.8 m2/g; and mean lengths and diameters of 5.8 μm and 158 nm, respectively. Four groups of rats per sex were exposed nose-only, 6 h/day, for 5 days/week to target concentrations of 0, 0.50, 2.5, or 25 mg/m3 VGCF-H over a 90-day period and evaluated 1 day later. Assessments included conventional clinical and histopathological methods, bronchoalveolar lavage fluid (BALF) analysis, and cell proliferation (CP) studies of the terminal bronchiole (TB), alveolar duct (AD), and subpleural regions of the respiratory tract. In addition, groups of 0 and 25 mg/m3 exposed rats were evaluated at 3 months postexposure (PE). Aerosol exposures of rats to 0.54 (4.9 f/cc), 2.5 (56 f/cc), and 25 (252 f/cc) mg/m. 3 of VGCF-H CNFs produced concentration-related small, detectable accumulation of extrapulmonary fibers with no adverse tissue effects. At the two highest concentrations, inflammation of the TB and AD regions of the respiratory tract was noted wherein fiber-laden alveolar macrophages had accumulated. This finding was characterized by minimal infiltrates of inflammatory cells in rats exposed to 2.5mg/m. 3 CNF, inflammation along with some thickening of interstitial walls, and hypertrophy/hyperplasia of type II epithelial cells, graded as slight for the 25mg/m. 3 concentration. At 3 months PE, the inflammation in the high dose was reduced. No adverse effects were observed at 0.54mg/m. 3. BALF and CP endpoint increases versus controls were noted at 25mg/m. 3 VGCF-H but not different from control values at 0.54 or 2.5mg/m. 3. After 90 days PE, BALF biomarkers were still increased at 25mg/m. 3, indicating that the inflammatory response was not fully resolved. Greater than 90% of CNF-exposed, BALF-recovered alveolar macrophages from the 25 and 2.5mg/m. 3 exposure groups contained nanofibers (> 60% for 0.5mg/m. 3). A nonspecific inflammatory response was also noted in the nasal passages. The no-observed-adverse-effect level for VGCF-H nanofibers was considered to be 0.54mg/m. 3 (4.9 fibers/cc) for male and female rats, based on the minimal inflammation in the terminal bronchiole and alveolar duct areas of the lungs at 2.5mg/m. 3 exposures. It is noteworthy that the histopathology observations at the 2.5mg/m. 3 exposure level did not correlate with the CP or BALF data at that exposure concentration. In addition, the results with CNF are compared with published findings of 90-day inhalation studies in rats with carbon nanotubes, and hypotheses are presented for potency differences based on CNT physicochemical characteristics. Finally, the (lack of) relevance of CNF for the high aspect ratio nanomaterials/fiber paradigm is discussed. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Seely J.C.,Experimental Pathology Laboratories Inc.
Journal of Toxicologic Pathology | Year: 2017
Nonclinical juvenile animal tests perform a valuable role in determining adverse drug effects during periods of organogenesis and/or functional maturation. Developmental anatomic and functional maturation time points are important to consider between juveniles and adults when regarding different organ toxicities in response to drug administration. The kidney is an example of a major organ that has differences in these time points in comparing juveniles to adults and in contrasting humans to laboratory animal species. Toxicologic pathologists, involved in juvenile studies, need to be aware of these time points which are age-related exposure periods of sensitivity to drug toxicity. Age-related developmental anatomic and functional maturation are factors which can affect the way that a drug is absorbed, distributed, metabolized, and excreted (ADME). Changes to any component of ADME may alter drug toxicity resulting in kidney abnormalities, nephrotoxicity, or maturational disorders. Juvenile animal kidneys may either be less resistant or more resistant to known adult nephrotoxic drug effects. Furthermore, drug toxicity observed in juvenile animal kidneys may not always correspond to similar toxicities in humans. Juvenile animal nonclinical toxicology studies targeting the kidneys have to be carefully planned to attain the maximum knowledge from each study. © 2017 The Japanese Society of Toxicologic Pathology.
Rao D.B.,Integrated Laboratory Systems, Inc. |
Little P.B.,Experimental Pathology Laboratories Inc. |
Sills R.C.,National Health Research Institute
Toxicologic Pathology | Year: 2014
This review article is designed to serve as an introductory guide in neuroanatomy for toxicologic pathologists evaluating general toxicity studies. The article provides an overview of approximately 50 neuroanatomical subsites and their functional significance across 7 transverse sections of the brain. Also reviewed are 3 sections of the spinal cord, cranial and peripheral nerves (trigeminal and sciatic, respectively), and intestinal autonomic ganglia. The review is limited to the evaluation of hematoxylin and eosin-stained tissue sections, as light microscopic evaluation of these sections is an integral part of the first-tier toxicity screening of environmental chemicals, drugs, and other agents. Prominent neuroanatomical sites associated with major neurological disorders are noted. This guide, when used in conjunction with detailed neuroanatomic atlases, may aid in an understanding of the significance of functional neuroanatomy, thereby improving the characterization of neurotoxicity in general toxicity and safety evaluation studies. © 2013 by The Author(s).
Maronpot R.R.,Experimental Pathology Laboratories Inc. |
Thoolen R.J.M.M.,Global Pathology Support |
Hansen B.,LPT Laboratory of Pharmacology and Toxicology
Experimental and Toxicologic Pathology | Year: 2015
Acrylamide is an important chemical with widespread industrial and other uses in addition to generalized population exposure from certain cooked foods. Previous rat studies to assess the carcinogenic potential of acrylamide have been carried out exclusively in the Fischer 344 rat with identification of a number of tumors amongst which mesotheliomas of the tunica vaginalis is an important tumor endpoint in the classification of acrylamide as a 'probably human carcinogen. In a rat carcinogenicity study to determine the human relevance of mesotheliomas Wistar Han rats were exposed to 0, 0.5, 1.5, or 3.0. mg acrylamide/kg body weight/day in drinking water starting at gestation day 6. At the end of two years, mammary gland fibroadenomas in females and thyroid follicular cell tumors in both sexes were the only tumors increased in acrylamide treated rats. These tumor endpoints have rat-specific modes of action suggesting less likelihood of human cancer risk than previously estimated. This study demonstrates that tunica vaginalis mesotheliomas are strain specific and not likely of genotoxic origin. © 2014 The Authors.
Steinbach T.J.,Experimental Pathology Laboratories Inc. |
Kane J.D.,Walter Reed Institute of Research
Veterinary Pathology | Year: 2013
Brunner's glands are submucosal glands located in the proximal duodenum. Hyperplasia of the Brunner's gland has been reported rarely in humans and animals. We examined sections of the Brunner's gland from 63 sand rats submitted for necropsy over 2 years. Of the 63 animals necropsied, 45 (71%) had evidence of hyperplasia defined as nodular expansion, dilated ducts, or intraductal papillary proliferation. The hyperplasia was graded as mild in 22 (49%) of the cases, moderate in 15 (33%), and marked in 8 (18%). We found an association with both increased age and evidence of gastric ulceration and hyperplasia of the Brunner's gland. In sand rats with marked hyperplasia, 8 of 8 (100%) had evidence of gastric ulceration, compared to 13 of 18 (72%) in animals with no hyperplasia. Animals with marked hyperplasia were, on average, 8.4 months older than animals with no hyperplasia. There was no association with gender. The lesion in sand rats is histologically similar to that in humans. © The Author(s) 2012.
Kent M.L.,Oregon State University |
Harper C.,Laboratory animal veterinarian |
Wolf J.C.,Experimental Pathology Laboratories Inc
ILAR Journal | Year: 2012
The zebrafish (Danio rerio) has become a very important animal model in biomedical research. In contrast with other models, such as mice, there has been relatively little documentation or control of subclinical disease in zebra-fish research facilities. Several infectious and noninfec-tious conditions are consistently detected by histopathology in apparently healthy D. rerio. The most commonly observed infectious agent in zebrafish is Pseudoloma neurophilia, which is a microsporidian organism that targets the central nervous system, peripheral nerves, and occasionally other tissues. Mycobacteriosis, caused by Mycobacterium chelo-nae and other species, is also a frequent finding. Less com-monly encountered agents include Pseudocapillaria tomentosa, which can cause extensive proliferative enteri-tis, and a myxozoan (Myxidium sp.) that inhabits the uri-nary tract but appears to cause few if any pathological changes. Noninfectious diseases that are often clinically unapparent in zebrafish include hepatic megalocytosis, bile and pancreatic ductal proliferation, and neoplasms of the ultimobranchial gland, gastrointestinal tract, and testis. To date, there is little information on the degree to which these conditions may impact research in subclinically affected fish, but there is reason to believe that they should be con-sidered as potentially significant causes of nonprotocol variation in experiments. Therefore, it is imperative that research facilities monitor their stocks for the presence of these occult diseases and be aware of their existence when interpreting study results. Furthermore, for underlying dis-ease conditions that cannot be readily eradicated, it is es-sential to determine the physiological and immunological changes that they elicit in zebrafish. Understanding the cause, modes of transmission, and distribution of the patho-gens would provide useful information for the develop-ment of control and prevention strategies.
Hardisty J.F.,Experimental Pathology Laboratories Inc.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association | Year: 2013
A thirteen week feeding study was conducted by feeding young adult male and female Sprague Dawley [Crl:CD®(SD)] rats diets containing grain from genetically modified (GM) DP-ØØ4114-3 maize that was either untreated (4114) or treated in the field with glufosinate ammonium (4114GLU). Control rats were fed diets containing the same concentration of near isogenic, non-GM maize grain (091) or one of three types of commercially available non-GM maize grain. At the end of the in-life phase, renal tubule tumors were reported in two male rats consuming diets containing 4114 maize grain. An expert panel of pathologists was convened as a Pathology Working Group (PWG) to review coded kidney histology sections from control (091) and treated (4114 and 4114GLU) male rats. The objectives were for the panel to characterize the histopathologic findings and to interpret their relationship to consumption of the indicated diet. The PWG concluded unanimously that the kidney tumors were characteristic of amphophilic-vacuolar (AV) tumors and AV atypical tubular hyperplasia which represent a distinctive phenotype that has been reported to occur sporadically in young Sprague Dawley Rats. The PWG determined that the neoplasms and atypical tubular hyperplasias were multicentric and bilateral which typifies tumors of familial origin. Degenerative/regenerative or cytotoxic changes consistent with nephrotoxicity leading to tumor induction were not observed in these rats and thus supports the conclusion that tumors were unrelated to consumption of the test diet. It was the unanimous opinion of the PWG that the proliferative renal tubule cell lesions were spontaneous and not related to consumption of diets containing 4114 maize grain.
Adams E.T.,Experimental Pathology Laboratories Inc.
Toxicologic pathology | Year: 2011
The 2010 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Chicago, Illinois, in advance of the scientific symposium sponsored jointly by the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP). The goal of the annual NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for voting or discussion. Some topics covered during the symposium included a comparison of rat and mouse hepatocholangiocarcinoma, a comparison of cholangiofibrosis and cholangiocarcinoma in rats, a mixed pancreatic neoplasm with acinar and islet cell components, an unusual preputial gland tumor, renal hyaline glomerulopathy in rats and mice, eosinophilic substance in the nasal septum of mice, INHAND nomenclature for proliferative and nonproliferative lesions of the CNS/PNS, retinal gliosis in a rat, fibroadnexal hamartoma in rats, intramural plaque in a mouse, a treatment-related chloracne-like lesion in mice, and an overview of mouse ovarian tumors.
Pandiri A.,Experimental Pathology Laboratories Inc.
Toxicologic Pathology | Year: 2015
Lung cancer is the number one cause of cancer-related deaths in humans worldwide. Environmental factors play an important role in the epidemiology of these cancers. Rodents are the most common experimental model to study human lung cancers and are frequently used in bioassays to identify environmental exposure hazards associated with lung cancer. Lung tumors in rodents are common, particularly in certain strains of mice. Rodent lung tumors are predominantly bronchioloalveolar carcinomas and usually follow a progressive continuum of hyperplasia to adenoma to carcinoma. Human lung cancers are phenotypically more diverse and broadly constitute 2 types: small cell lung cancers and nonsmall cell lung cancers (NSCLCs). Rodent lung tumors resulting from exposure to environmental agents are comparable with certain adenocarcinomas that are a subset of human NSCLCs. Human pulmonary carcinomas differ from rodent lung tumors by exhibiting greater morphologic heterogeneity (encompassing squamous cell, neuroendocrine, mucinous, sarcomatoid, and multiple cell combinations), higher metastatic rate, higher stromal response, aggressive clinical behavior, and lack of a clear continuum of proliferative lesions. In spite of these differences, rodent lung tumors recapitulate several fundamental aspects of human lung tumor biology at the morphologic and molecular level, especially in lung cancers resulting from exposure to environmental carcinogens. © 2014 by The Author(s).
Pandiri A.R.,Experimental Pathology Laboratories Inc
Toxicologic Pathology | Year: 2014
Exocrine pancreas is a source of several enzymes that are essential for the digestive process. The exocrine pancreatic secretion is tightly regulated by the neuroendocrine system. The endocrine pancreas is tightly integrated anatomically and physiologically with the exocrine pancreas and modulates its function. Compound-induced pancreatitis is not a common event in toxicology or drug development, but it becomes a significant liability when encountered. Understanding the species-specific differences in physiology is essential to understand the underlying pathobiology of pancreatic disease in animal models and its relevance to human disease. This review will mainly focus on understanding the morphology and physiology of the pancreas, unique islet-exocrine interactions, and pancreatitis. © 2013 by The Author(s).