As biotechnology companies continue to develop immunomodulatory compounds, more often than not, the only relevant species for preclinical safety assessment is the non-human primate (NHP). Toxicology pathologists are increasingly evaluating tissues from preclinical safety assessment studies conducted in the NHP, mainly the cynomolgus monkey but occasionally the rhesus monkey and common marmoset. A basic understanding of the spontaneous infections and opportunistic pathogens that can arise in NHPs is important when evaluating compounds that ultimately can affect the integrity and function of the immune system. This chapter provides a brief overview on the pathological characteristics of the most common infections and pathogens that can occur in NHP in the research settings.

The respiratory system is a complex association of organs and anatomic structures, responsible for the vital function of gas exchanges, bringing oxygen to the blood and removing the carbon dioxide from it. This complexity is more evident in the upper part of the respiratory system with a large diversity in anatomical structures across species; further down into the bronchi and lung, species-specific anatomical variations are less evident, yet still exist. The knowledge of those differences is important, when dealing with toxicological changes in the respiratory system, and of paramount importance in inhalation studies. The use of non-human primates (NHP) in toxicology has been increasing in the past decades, in line with the expansion of biologics in the therapeutic area of inhalation, which often requires NHP as the pharmacologically relevant species to be tested. The exposure to the external environment and to the internal blood circulation makes the respiratory system particularly prone to develop lesions, spontaneously or due to administered materials. The lesions can range from degenerative to inflammatory as well as to proliferative.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions Project (www.toxpath.org/inhand.asp) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and non-proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in most tissues and organs from the laboratory rabbit used in nonclinical safety studies. Some of the lesions are illustrated by color photomicrographs. 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 lesions as well as lesions induced by exposure to test materials. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature for lesions in laboratory animals will provide a common language among regulatory and scientific research organizations in different countries and increase and enrich international exchanges of information among toxicologists and pathologists.

Toxicologic Pathology is the official journal of the Society of Toxicologic Pathology (STP), the British Society of Toxicological Pathology, and the European STP (ESTP). Toxicologic Pathology publishes articles related to topics in various aspects of toxicologic pathology such as anatomic pathology, clinical pathology, experimental pathology, and biomarker research. Publications include society-endorsed Best Practice/Position and Points to Consider publications and ESTP Expert Workshop articles that are relevant to toxicologic pathology and scientific regulatory processes, Opinion articles under the banner of the STP Toxicologic Pathology Forum, Original Articles, Review Articles (unsolicited/contributed, mini, and invited), Brief Communications, Letters to the Editor, Meeting Reports, and Book Reviews. This article provides details on the various publication categories in Toxicologic Pathology and will serve as a reference for authors and readers.

This study was conducted to characterize lung microscopic lesions in control beagle dogs from inhalation and oral gavage toxicity studies, to determine differences associated with the route of administration, and to discuss distinguishing features from compound-induced lung lesions. Samples from 138 control dogs from oral gavage studies and 124 control dogs from inhalation (vehicle control) studies were evaluated microscopically. There was no significant sex-related difference in the incidence of all lesions. Perivascular mononuclear cell infiltration, centriacinar mixed cell infiltration, bronchopneumonia, subpleural septal fibrosis, and alveolar macrophage accumulation were the most common lesions. Aspiration pneumonia was more common in dogs from gavage studies, suggesting reflux after gavage dosing or accidental administration of test formulation as possible causes. Centriacinar mixed cell infiltration was more common in dogs from inhalation studies, suggesting mild irritation by the vehicles used. Vascular lesions, which included pulmonary arteriopathy and smooth muscle mineralization, were observed in a few animals. Some of the spontaneous lesions are similar to lesions induced by test compounds. Compared to spontaneous lesions, compound-induced lesions tend to be multifocal or diffuse, follow a pattern of distribution (e.g., centriacinar, perivascular, and interstitial), show a dose response in the incidence and severity, and may show cell-specific toxicity.