Proliferative and Non-Proliferative Lesions of the Rat and Mouse Integument

Abstract

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the societies of toxicological pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP). Its aim is to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory rodents. A widely accepted international harmonization of nomenclature in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and will provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. The purpose of this publication is to provide a standardized nomenclature for classifying microscopical lesions observed in the integument of laboratory rats and mice. Example colour images are provided for most lesions. The standardized nomenclature presented in this document and additional colour images are also available electronically at http://www.goreni.org. The nomenclature presented herein is based on histopathology databases from government, academia, and industrial laboratories throughout the world, and covers lesions that develop spontaneously as well as those induced by exposure to various test materials. (DOI: 10.1293/tox.26.27S; J Toxicol Pathol 2013; 26: 27S–57S)

Heavy metal–induced toxicity in the Indian green frog: Biochemical and histopathological alterations

“…In contrast, marginal histopathological manifestations with 1 to 2 foci affected by degeneration of epithelia and necrosis were evident in frogs from the polluted site (histopathological score 0.59 AE 0.11; S ¼ 5.37, p ¼ 0.05, ANOVA; Figure 9C and D), while laboratory exposed frogs had an elevated score of 1.68 AE 0.09 (p ¼ 0.001). As described by Mecklenburg et al [41], loss of cilia in the respiratory epithelium, epithelial blebbing or cytoplasmic vacuolation, and rounding up of the cells were evident in metal-exposed frogs.…”

Drug-Induced Cutaneous Toxicity

“…Microsomal enzymes in keratinocytes are capable of metabolizing topically applied chemicals, thus rendering them inactive or active. Dimethylbenz(a)anthracene (DM"") becomes a potent skin carcinogen after metabolic activation by keratinocytes [11]. Note that scalp, inguinal, and abdominal skin are thin.…”

“…"ctivation of mast cells, complement or prostaglandin synthesis results in reversible damage to the skin, observed as irritation within hours following topical application of the chemicals. Irritant dermatitis is characterized by inlammatory cell iniltration, acanthosis, epidermal hyperkeratosis, and hyperplasia associated with other epidermal changes such as erosion/ulcer, necrosis, or vesicle formation [11]. Irritant dermatitis depends on the severity of the irritants and duration of their exposures [5, ] (Figure ).…”

“…Irritant dermatitis depends on the severity of the irritants and duration of their exposures [5, ] (Figure ). If the damage to the skin is irreversible, the lesion is clinically referred to as corrosion, which is characterized by full thickness necrosis of the epidermis penetrating into the underlying dermis [11]. In preclinical studies of topical application agents, skin irritation testing is conducted using rabbits or guinea pigs to evaluate drug-induced irritation using the Draize method (with a 5-grade score based on macroscopic assessment of the severity of erythema, crusting, and edema) (Figure and The mechanism remains unknown, although an allergic reaction has been speculated.…”

“…Chemical-induced acne is a disease of hair follicles caused by a chemical substance and is characterized by keratin plugs in hair follicles due to excessive proliferation of keratinocytes in hair follicles (comedo), sebum retention and inlammation [11]. Known examples of chemical-induced acne include occupational skin disorders of oil acne, caused by frequent exposure of the skin to cuting oils, as well as chloracne, induced by dioxins such as TCDD and PC" [15].…”