Revised guides for organ sampling and trimming in rats and mice--Part 3. A joint publication of the RITA and NACAD groups.

This is the third part of a series of three articles on trimming instructions of rat and mouse protocol organs and tissues in regulatory type toxicity studies, covering the urinary, nervous, musculoskeletal, cardiovascular, and lymphoreticular systems. The article is based on the experience of the European RITA and American NACAD working groups and is an extended revision of trimming guides published in 1995 (BAHNEMANN et al.). The optimum localization for tissue preparation, the sample size, the direction of sectioning and the number of sections to be prepared is described organ by organ. These descriptions are illustrated for each organ by a schematic drawing and/or a macro-photograph showing the plane of section as well as a low magnification of the H&E stained slide demonstrating the optimum "end-product". The objectives of this work, as addressed in detail in the first part (Ruehl-Fehlert et al. 2003), are to standardize tissue sampling and trimming for comparison of historical data obtained from different studies and different laboratories, ensure the presence of all relevant target sites for histopathological evaluation and provide technical advice for preparatory techniques during necropsy, fixation and trimming (Crissman et al. 2004).

Revised guides for organ sampling and trimming in rats and mice--Part 2. A joint publication of the RITA and NACAD groups.

This is the second part of a series of three articles on trimming instructions of rat and mouse protocol organs and tissues in regulatory type toxicity studies, covering the respiratory, male and female genital, and the endocrine systems. The article is based on the experience of the European RITA and American NACAD working groups and is an extended revision of trimming guides published in 1995 (Bahnemann et al.). The optimum localization for tissue preparation, the sample size, the direction of sectioning and the number of sections to be prepared is described organ by organ. These descriptions are illustrated for each organ by a schematic drawing and/or a macro-photograph showing the plane of section as well as a low magnification of the H&E stained slide demonstrating the optimum "end-product". The objectives of this work, as addressed in detail in the first part (Ruehl-Fehlert et al. 2003), are to standardize tissue sampling and trimming, to improve the comparability of historical data obtained from different studies and different laboratories, ensure the presence of all relevant target sites for histopathological evaluation and provide technical advice for preparatory techniques during necropsy, fixation and trimming. dardize tissue sampling and trimming, to improve the comparability of historical data obtained from different studies and different laboratories, ensure the presence of all relevant target sites for histopathological evaluation and provide technical advice for preparatory techniques during necropsy, fixation and trimming.

Revised guides for organ sampling and trimming in rats and mice--part 1.

This is the first part of a series of three articles on trimming instructions of rat and mouse protocol organs and tissues in regulatory type toxicity studies. It is based on the experience made in the European RITA and American NACAD working groups and is an extended revision of trimming guides published in 1995 (Bahnemann et al.). The optimum localization for tissue preparation, the sample size, the direction of sectioning and the number of sections to be prepared is described organ by organ. These descriptions are illustrated for each organ by a schematic drawing and a macro-photograph showing the plane of section as well as a low power view of the H&E stained slide demonstrating the optimum "end-product". This revision will improve the quality and efficiency of routine procedures and facilitate daily work in the histotechnical lab. It will promote intra- and inter-study reproducibility and comparability and thus lead to a further coherence within each study and improvement of the validity of historical control data.

The north american control animal database: a resource based on standardized nomenclature and diagnostic criteria.

Historical control data have been shown to be valuable in the interpretation and evaluation of results from rodent carcinogenicity studies. Standardization of terminology and histopathology procedures is a prerequisite for meaningful comparison of control data across studies and analysis of potential carcinogenic effects. Standardization is particularly critical for the construction of a database that includes incidence data from different studies evaluated by pathologists in different laboratories. Standardized nomenclature and diagnostic criteria have been established for neoplasms and proliferative lesions. Efforts of the National Toxicology Program, the Society of Toxicologic Pathology (STP), and the Registry of Industrial Toxicology Animal-data (RITA) have led to a harmonized pathology nomenclature for the rat and the mouse. This nomenclature with detailed descriptions of lesions is available in publications by the STP and International Agency for Research on Cancer (IARC). A listing of these terms is available on the World Wide Web. Utilizing the model established by RITA and working with the International Life Sciences Institute (ILSI), companies with laboratories in North America formed a working group in 1994 to establish and maintain a database of neoplastic and proliferative lesions from control animals in carcinogenicity studies. The rationale for development of the North American Control Animal Database (NACAD), the factors that influence tumor incidence, operation of the database, and the benefits to be realized by using a standardized approach are discussed.

The value of historical control data-scientific advantages for pathologists, industry and agencies.

Historical control tumor data are useful in the interpretation of long-term rodent carcinogenicity bioassays, especially to assess the occurrence of rare tumors and marginally increased tumor incidences. The major prerequisites to compare historical control data with studies under evaluation are the validity and consistency of the respective databases. The RITA (Registry of Industrial Toxicology Animal-data) database for historical data of tumors and pre-neoplastic lesions collects data according to highly standardized procedures including tissue sampling and trimming, histopathology according to internationally harmonized nomenclature and diagnostic criteria, and peer review. All lesions that are entered are unanimously diagnosed according to IARC (Intermational Agency for Research on Cancer)/WHO criteria. The validity of data is additionally confirmed by a complete peer review performed by a database pathologist. Equivocal diagnoses and selected cases are additionally submitted to a panel of RITA pathologists. In the RITA database, there are currently 10,896 rats from 106 studies with more than 17,604 primary tumors and 16,551 pre-neoplastic lesions. The RITA database for historical control data for Wistar and Sprague Dawley rats as well as for different mouse strains is briefly described. Based upon RITA background data, the survival rate of Wistar rats has been consistent over a period of 10 years. The occurrence of tumor-bearing animals also shows a stable percentage over a decade. Additionally, examples of how historical control data may support carcinogenic risk assessment in cases of rare tumors or marginally increased incidences of tumors and pre-neoplastic lesions are given.