Idiopathic Aneurysms of the Ascending Aorta in the Mouse and Rat.

Aneurysms of the ascending aorta, unrelated to xenobiotic administration, are described in 5 rats and 2 mice in nonclinical safety studies conducted at Charles River Laboratories (CRL) sites over the past 10 years. The most prominent microscopic finding was focal dilation with disruption of the wall of the ascending aorta with chronic adventitial inflammation or fibroplasia. The pathogenesis of this finding is unknown.

Dissection of the Trigeminal Ganglion of Nonrodent Species Used in Toxicology Studies.

The ganglion of the trigeminal (V cranial) nerve is generally sampled at necropsy in nonrodent toxicology studies only when somatic or autonomic peripheral nervous system toxicity is suspected. The ganglion is far more difficult to locate in nonrodents than in rats and mice, and suitable methods to dissect it have been described only for swine. The trigeminal nerve caudal to the ganglion passes through a canal, roofed by bone in dogs and rabbits and by a tough layer of dura mater in swine and nonhuman primates.

Review of Sexual Maturity in the Minipig.

It is important to know whether the animals used in toxicology studies are sexually mature. As minipigs are being used increasingly in toxicity studies, we reviewed published data on the age of sexual maturity in the minipig. Maturity in females was assessed on the basis either of normal cycles of progesterone secretion or of the histological presence of corpora lutea and, in males, was assessed on the histological appearance of the seminiferous tubules and epididymides.

Spontaneous testicular tubular hypoplasia/atrophy in the Göttingen minipig: a retrospective study.

The aim of this retrospective study was to assess the incidence and severity of tubular atrophy/hypoplasia in the testes of 104 control Göttingen minipigs aged 4.5 to 15 months. The finding was termed "tubular hypoplasia/atrophy" according to published descriptions for the dog.

Onset of puberty and normal histological appearances of the reproductive organs in peripubertal female Göttingen minipigs.

In preclinical studies, it is important to know whether the animals used are sexually mature or not. Precise data have not yet been published, however, about the histological features of the female reproductive organs during the peripubertal period or about the age of acquisition of sexual maturity in the minipig. The histological characteristics of the genital organs of female control minipigs from toxicology studies were described and, based on the presence of ovarian corpora lutea, used to assess the age at which maturity was reached.

Apparent alveolar bronchiolar tumors arising in the mediastinum of F344 rats.

Rare tumors were observed in chronic studies in F-344 rats that were purely or largely free in the mediastinal cavity, yet had the histological architecture of alveolar bronchiolar tumors. They had originally been diagnosed as either pulmonary alveolar bronchiolar tumors, mediastinal mesotheliomas, or thymomas. The authors described these tumors, estimated the fraction of thoracic tumors that they represented, and carried out a preliminary immunohistochemical investigation of whether they were of pulmonary or mesothelial origin.

Histopathological lesions following intramuscular administration of saline in laboratory rodents and rabbits.

This review was undertaken to assess the nature and incidence of procedure-related changes in mice, rats and rabbits which received saline solution by intramuscular injection. Data were collected on the injection sites from 7 studies representing 152 animals. The original observations by the different study pathologists from both control and treated animals were evaluated in order to create a glossary of preferred terms to be used in toxicology studies.

Variability in weight and histological appearance of the prostate of beagle dogs used in toxicology studies.

This review was performed to assess variations in weight and histologic appearance of the prostate of untreated male beagle dogs between 23 and 108 weeks of age, from two breeding centers. Data from 125 control beagle dogs from twenty-seven regulatory toxicology studies were used. Age, terminal body weight, and prostate weight were analyzed.

Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys.

Background: Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation.

Morphology of the fetal rat testis preserved in different fixatives.

Histopathological examination of the testes of exposed fetuses and neonates is important in assessing the developmental effects of environmental toxins, including sex hormone modulators. Modified Davidson's fluid (mDF) has been suggested as a superior substitute for Bouin's fluid for fixation of adult animal testes. We compared the morphology of fetal rat testes stained with hematoxylin and eosin (H&E) or immunochemically after fixation in 10% neutral buffered formalin (NBF), Bouin's fluid, or mDF.

Decreased longevity and enhancement of age-dependent lesions in mice lacking the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha).

The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is activated by peroxisome proliferators (PP), a large class of structurally diverse xenobiotic chemicals, hypolipidemic drugs, and endogenous lipids. PPARalpha alters the transcriptional programs of genes whose functions include lipid metabolism, inflammation, cell fate, and stress responses in liver, heart, kidney, and skin. Many of these genes are also under control of PPARalpha in the absence of exogenous peroxisome proliferator exposure.

The transcriptional response to a peroxisome proliferator-activated receptor alpha agonist includes increased expression of proteome maintenance genes.

The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha), in addition to regulating lipid homeostasis, controls the level of tissue damage after chemical or physical stress. To determine the role of PPARalpha in oxidative stress responses, we examined damage after exposure to chemicals that increase oxidative stress in wild-type or PPARalpha-null mice. Primary hepatocytes from wild-type but not PPARalpha-null mice pretreated with the PPAR pan-agonist WY-14,643 (WY) were protected from damage to cadmium and paraquat.

Role of the peroxisome proliferator-activated receptor alpha (PPARalpha) in responses to trichloroethylene and metabolites, trichloroacetate and dichloroacetate in mouse liver.

Trichloroethylene (TCE) is an industrial solvent and a widespread environmental contaminant. Induction of liver cancer in mice by TCE is thought to be mediated by two carcinogenic metabolites, dichloroacetate (DCA) and trichloroacetate (TCA). TCE is considered to be a relatively weak peroxisome proliferator (PP), a group of rodent hepatocarcinogens that cause adaptive responses in liver through the PP-activated receptor alpha (PPARalpha).