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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).


Clewell R.A.,Hamner Institutes for Health Sciences | Thomas A.,Hamner Institutes for Health Sciences | Willson G.,Experimental Pathology Laboratories Inc. | Creasy D.M.,Huntingdon Life science | Andersen M.E.,Hamner Institutes for Health Sciences
Reproductive Toxicology | Year: 2013

Male rat sexual development was evaluated after dietary administration of 0, 760, 3800, 11,400. ppm diisononyl phthalate (DiNP) and 7600. ppm dibutyl phthalate (DBP) from gestation day (GD) 12 to postnatal day (PND) 14. Maternal weight was reduced on GD 20, PND 2 and 14 at 11,400. ppm DiNP. Pup weight was reduced on PND 2 and 14 at 11,400 and 3800. ppm DiNP. DBP induced multinucleated germ cells (MNGs) and Leydig cell aggregates (LCAs) in PND 2 testes. 7600. ppm DBP reduced anogenital distance (AGD) on PND 2 and 14, and increased nipple retention and reproductive tract malformations on PND 49. DiNP induced MNGs (3800. ppm) and LCAs (11,400. ppm) on PND 2, and reduced AGD (11,400. ppm) on PND 14. DiNP did not alter AGD, nipple retention or reproductive tract malformations on PND 49. Global endpoint analysis showed no evidence of a rat " phthalate syndrome" on PND 49 with DiNP administration. © 2012 Elsevier Inc.


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.


Nikula K.J.,Seventh Wave Laboratories LLC | Funk K.,Experimental Pathology Laboratories Inc.
Toxicologic Pathology | Year: 2016

Necropsies conducted to support medical device development may be conducted in facilities that do not have the infrastructure in place to support Good Laboratory Practice for Nonclinical Laboratory Studies (GLP) studies and for a variety of reasons they may be conducted without a pathologist present at necropsy. However, when a novel medical device or one that is expected to significantly alter tissues is deployed, or when the surgical model confounds interpretation of device effects, it is the opinion of the authors that an experienced pathologist should be present at necropsy. © The Author(s) 2015.


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).

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