The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the female reproductive tract of laboratory rats and mice, with color photomicrographs illustrating examples of some lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. There is also a section on normal cyclical changes observed in the ovary, uterus, cervix and vagina to compare normal physiological changes with pathological lesions. A widely accepted and utilized international harmonization of nomenclature for female reproductive tract lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

Many compounds giving a positive result in animal carcinogenicity studies through mechanisms involving secondary carcinogenesis pose little or no risk to humans. This article provides an overview of current understanding, with particular reference to renal tumors in male rats with cu,,-globulin nephropathy, urinary bladder neoplasia in rodents, mesovanan leiomyomas induced in rats by &-receptor stimulants, carcinoid tumors in the rodent stomach induced by prolonged suppression of acid secretion, thyroid follicular cell tumors in rodents, canine mammary neoplasia due to administration of progestagens, rodent mammary neoplasia induced by estrogens, uterine endometrial carcinomas of rats induced by dopamine agonists, Leydig cell tumors in the testis of rats, and ovarian tubulostromal adenomas in mice. A positive result on a rodent carcinogenicity study should not automatically preclude further development of a compound; future progress in this field should increase the accuracy of the rodent carcinogenicity study as a tool in human safety assessment.

In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Differences between each test group and the control group were evaluated. Equivalence was assessed by comparing the observed difference to differences between non-GM reference groups in previous studies. In case of significant differences, whether the effects were dose-related and/or accompanied by changes in related parameters including histopathological findings was evaluated. It is concluded that no adverse effects related to the feeding of the NK603 maize cultivated with or without Roundup for up to 2 years were observed. Based on the outcome of the subchronic and combined chronic toxicity/carcinogenicity studies, recommendations on the scientific justification and added value of long-term feeding trials in the GM plant risk assessment process are presented.

spinal cord and comments on posterior paralysis. JNCI 26: 7719-735 Kalimo H, Lehto M, Nanto-Salonen !<., Jalkanen M, Risteli L, Risteli J, Narva EV (1985) Characterization of the perivascular reticulin network in a case of primary brain lymphoma. Krinke G, Naylor DC, Schmid S, Frohlich E, Schnider K (1985) The incidence of naturally-occurring primary brain tumours in the laboratory rat. J Comp Pat hoi 95: 175-192 Luginbuhl H (1963) Comparative aspects of tumors of the nervous system. Ann NY Acad Sci 108: 702-721 Luginbuhl H, Fankhauser R, McGrath JT (1968) Spontaneous neoplasms of the nervous system in animals.

Abstract. Ninety-six primary cardiac neoplasms were identified from 79,97 1 Fischer 344 (F344) rats used in chronic toxicity and carcinogenicity studies by the National Toxicology Program (NTP) and National Cancer Institute (NCI), for an overall incidence of 0.1%. Neoplasms were classified as: 60 endocardial schwannomas, 23 intramural schwannomas, eight atriocaval mesotheliomas, three paragangliomas, one pericardial mesothelioma, and one hemangioma. Metastases occurred in four rats with endocardial schwannoma. Histological appearance of the endocardial and intramural schwannomas was consistent with origin from nerve sheath. Two of six endocardial schwannomas available for immunohistochemical staining were weakly positive for S-100 antigen. The atriocaval mesotheliomas, while morphologically resembling adenocarcinoma, were positive for vimentin and keratin, indicating mesothelial origin. Seventy of the 96 cardiac neoplasms occurred in rats 2 years of age or older at time of death. There were no sex or treatment-related differences in the incidence of these neoplasms, with the exception of atriocaval mesothelioma, which was more common in males.Spontaneous primary cardiac neoplasms are rare in rats with the exception of congenital atriocaval mesothelioma, which occurs in 20% of NZWGd inbred albino rats.13 Because of this low incidence, many documented cardiac neoplasms are individual case reports or incidental findings in publications on another subject. The literature on rat cardiac neoplasms is complicated by different terminology and by disagreement about cell of origin. Endocardia1 neoplasm^^^,^^ of rats have previously been referred to as endocardial disease,4 sub-endocardial endocardial mesenchymal neoplasm,2o endocardial ~c h w a n n o m a ,~.~~ neur i n o r n a~,~~ n e u r i l e m~m a s ,~~ neurosar~ornas,~~ and Anitschkow cell sarcomas.36 Intramural schwanno ma^^,^^ have also been reported as neurilemoma2* and fibroma.38 Atriocaval neoplasm^^^-^^ have previously been reported in NZWGd rats as epithelial or mesothelial neoplasms. Paragangliomas ("chemodecto ma^"),^.^^ pericardial m e s o t h e l i o m a~, I~,~~,~~ and hemangioma~~~.~* have also been reported in rats. Terminology used in this report is based on that used in a recent review of comparative pathology of cardiac neoplasms in humans and laboratory rodents.2o Although many previous reports of rat cardiac neoplasms contain detailed accounts of light and electron microscopic morphology, they are generally confined to a single neoplasm type, and it is seldom possible to assess neoplasm incidences, as the total population at risk is not stated.The purpose of this paper is to establish the incidence of cardiac neoplasms in a large population of Fischer 344 rats, to compare and contrast morphological and immunohistochemical features, and to clarifL the controversial origin of these neoplasms. Materials and MethodsNeoplasms were identified by histological examination of Fischer 344 (F344) rats from over 300,2-year toxicology and carcinogenicity studies ...