Electronic imaging system incorporating a hand-held fundus camera for canine ophthalmology.

An electronic imaging system incorporating a hand-held fundus camera was used to collect images of the canine ocular fundus. The electronic imaging system comprised a hand-held fundus camera, an IBM personal computer (PC 350), Microsoft Windows NT 4.0, Adobe Photoshop, and a color printer (Tektronix Phaser 550) and was used to store, edit, and print the images captured by the fundus camera. Hand-held fundus cameras are essential for use in canine ophthalmology. The Nidek NM-100 hand-held fundus camera digitalizes images, enabling their direct transfer into reports and their storage on writeable CDs.

Renaut bodies in the sciatic nerve of beagle dogs.

182 control Beagle dogs from 23 historical studies (14 chronic, 9 subchronic) were reviewed histologically for the presence of Renaut bodies in the sciatic nerve. Renaut bodies were found in 36.1 percent of the subchronic-study dogs and in 46.4 percent of the chronic-study dogs. The Renaut bodies most often resided in the distal sections of the sciatic nerve, specifically in the tibial branch as it traversed the knee joint in situ. There was no sex predilection. Renaut bodies were located predominately in the endoneurium, in the center of the nerve sections. There was no associated axonal degeneration, reactive gliosis, or encapsulation. The Renaut bodies were characterized as large (20 to 500 microns diameter in cross section), well-demarcated elliptical structures with an onion-skin arrangement of loosely textured, filamentous strands intermixed with sparse numbers of dark spindle-shaped nuclei. Occasionally the core displayed a more dense, intensely eosinophilic arrangement of fibers. Histochemical results included: positive acidic alcian blue, Gomori's trichrome, and Verhoeff Van Gieson's; and negative Periodic-acid Schiff, Congo Red, and Luxol fast blue/cresyl violet. Immunohistochemical results included: positive vimentin and collagen (subtypes I, II, and VI); and negative NSE, S-100, GFAP, amyloid A component, desmin, alpha-sarcomeric actin, pancytokeratin, EMA, and von Willebrand factor. Transmission electron microscopy revealed loosely arrayed, circumferentially oriented collagen fibers intermixed with varying amounts of amorphous substance and finely fibrillar material. Most of the cells comprising the Renaut body were identified as fibroblasts. No nerve fibers entered or left the Renaut body, and nearby nerves appeared to be normal structurally. Based on this characterization of Renaut bodies and in conjunction with the past literature, Renaut bodies appear to have little or no pathological significance, but rather are suggestive of a physiological adaptation in response to mechanical stress imposed on nerves.

Tumors in long-term rat studies associated with microchip animal identification devices.

Tumors surrounding implanted microchip animal identification devices were noted in two separate chronic toxicity/oncogenicity studies using F344 rats. The tumors occurred at a low incidence rate (approximately 1 percent), but did result in the early sacrifice of most affected animals, due to tumor size and occasional metastases. No sex-related trends were noted. All tumors occurred during the second year of the studies, were located in the subcutaneous dorsal thoracic area (the site of microchip implantation) and contained embedded microchip devices. All were mesenchymal in origin and consisted of the following types, listed in order of frequency: malignant schwannoma, fibrosarcoma, anaplastic sarcoma, and histiocytic sarcoma. The following diagnostic techniques were employed: light microscopy, scanning electron microscopy, and immunohistochemistry. The mechanism of carcinogenicity appeared to be that of foreign-body induced tumorigenesis.

Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat.

BACKGROUND: 1,6-Hexamethylene diisocyanate (HDI), a widely used chemical in commercial polyurethane manufacture, has been shown to affect the respiratory tract of experimental animals. However, its potential to affect neonatal development, particularly after inhalation exposure, is less well described. The present study was conducted to assess the developmental toxicity of HDI. METHODS: Gravid Sprague-Dawley rats were exposed to concentrations of 0, 0. 005, 0.050, or 0.300 ppm HDI via inhalation (whole-body exposure) on days 0-19 of gestation. Maternal toxicity, as demonstrated by clinical signs and changes in body weight gain during gestation, was characterized. Dams were sacrificed on gestation day 20, at which time fetuses were removed by cesarean section, the uterus was examined, and a gross maternal necropsy was performed. Maternal evaluation also included lung weight and a detailed histopathologic assessment of the nasal turbinates, larynx, trachea, and lungs. All fetuses were evaluated for external anomalies. Approximately one-half of each litter was examined for visceral effects, the other half underwent a skeletal (bone and cartilage) examination. RESULTS: Maternal toxicity was demonstrated in the 0.300- and, to a lesser extent, in the 0.050-ppm exposure groups. No maternal effects were noted in the 0.005-ppm group. Test compound-related maternal effects were restricted to histopathological findings and included acanthosis, hyperkeratosis, inflammation of the nasal turbinates, and, more seriously, degeneration of the olfactory epithelium. No pathological alterations were noted in the larynx, trachea, or lungs in any dose group. No test compound-related effects were observed on any reproductive parameters, or any embryonic endpoints, including pre/postimplantation loss and resorption. There were no effects on litter size or the number of fetuses per implantation site and no effects on fetal or placental weights were observed. No test compound-related fetal external, visceral, or skeletal findings were observed. No effect on the fetal or litter incidence of total malformations or variations was observed, and there was no difference in the incidence of malformations between males and females. CONCLUSIONS: Administered as described in this study, 1, 6-HDI produced maternal effects (nasal turbinate histopathology) at concentrations of 0.050 and 0.300 ppm with no developmental toxicity observed at any concentration.

Chronic toxicity and carcinogenicity testing in the Sprague-Dawley rat of a prospective insect repellant (KBR 3023) using the dermal route of exposure.

The chronic toxicology and carcinogenic potential of 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)-piperidine (KBR 3023), a prospective new insect repellent intended for human use, was studied in rats using the dermal route of application. Relying upon the toxicology profile that emerged in the subchronic rat bioassay that was conducted using dermally applied dosages of 0, 80, 200, 500 and 1000 mg KBR 3023/kg body wt/day, it was determined, in concert with the Environmental Protection Agency (EPA), that dermally applied dosages of 0, 50, 100 or 200 mg KBR 3023/kg body wt/day would be used in the conduction of all definitive forms of subchronic, chronic, and lifetime descriptive testing performed with the chemical. Using this testing approach, the specific results of this 2-year study are as follows. All in-life parameters, which included body weight, food consumption, clinical observations, survival, ophthalmology, clinical chemistry, hematology, and urinalysis, were unaffected by exposure to KBR 3023. Similarly, postmortem analyses, which included organ weights and gross pathology, were also unchanged following exposure to KBR 3023. Histopathology at the dose site/skin was characterized by a pattern of acanthosis and/or hyperkeratosis across all doses in 1- and 2-year rats. Beyond the dosing site, cystic degeneration of the liver was described in 2-year 200-mg KBR 3023/kg body wt/day males. No other compound-related non-dosing site lesion was identified at any dose tested. No evidence of a compound-induced neoplasia was suggested in this bioassay.

Urinary physiologic and chemical metabolic effects on the urothelial cytotoxicity and potential DNA adducts of o-phenylphenol in male rats.

ortho-Phenylphenol (OPP), a fungicide and antibacterial agent with food residues, is carcinogenic to rat bladder. The present studies provide information on changes in urinary composition and urinary metabolites, urothelial cytotoxicity and regenerative hyperplasia, and DNA adducts in male F344 rats fed OPP. An initial experiment evaluated dietary doses of 0, 1,000, 4,000, and 12,500 ppm OPP fed for 13 weeks. There was no evidence of urinary calculi, microcrystalluria, or calcium phosphate-containing precipitate, but urothelial cytotoxicity and hyperplasia occurred at the highest dose only. In a second experiment, rats were fed dietary OPP levels of 0, 800, 4,000, 8,000, and 12,500 ppm. Urinary pH was > 7 in all groups. Urinary volume was increased at the 2 highest doses with consequent decreases in osmolality, creatinine, and other solutes. Total urinary OPP metabolite excretions were increased, mostly excreted as conjugates of OPP and of phenylhydroquinone. Free OPP or free metabolites accounted for less than 2% excreted in the urine without a dose response. Urothelial toxicity and hyperplasia occurred only at doses of 8,000 and 12,500 ppm. OPP-DNA adducts were not detected in the urothelium at any dose. In summary, OPP produces cytotoxicity and proliferation of the urothelium at dietary doses > or = 8,000 ppm without formation of urinary solids. The paucity of unconjugated metabolites and the lack of OPP-DNA adducts suggests that OPP is acting as a bladder carcinogen in male rats by inducing cytotoxicity and hyperplasia without it or its metabolites directly binding to DNA.

Evidence of chemical stimulation of hepatic metabolism by an experimental acetanilide (FOE 5043) indirectly mediating reductions in circulating thyroid hormone levels in the male rat.

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3, 4-thiadiazol-2-yl]oxy]acetamide (FOE 5043) is a new acetanilide-type herbicide undergoing regulatory testing. Previous work in this laboratory suggested that FOE 5043-induced reductions in serum thyroxine (T4) levels were mediated via an extrathyroidal site of action. The possibility that the alterations in circulating T4 levels were due to chemical induction of hepatic thyroid hormone metabolism was investigated. Treatment with FOE 5043 at a rate of 1000 ppm as a dietary admixture was found to significantly increase the clearance of [125I]T4 from the serum, suggesting an enhanced excretion of the hormone. In the liver, the activity of hepatic uridine glucuronosyl transferase, a major pathway of thyroid hormone biotransformation in the rat, increased in a statistically significant and dose-dependent manner; conversely, hepatic 5'-monodeiodinase activity trended downward with dose. Bile flow as well as the hepatic uptake and biliary excretion of [125I]T4 were increased following exposure to FOE 5043. Thyroidal function, as measured by the discharge of iodide ion in response to perchlorate, and pituitary function, as measured by the capacity of the pituitary to secrete thyrotropin in response to an exogenous challenge by hypothalamic thyrotropin releasing hormone, were both unchanged from the controlled response. These data suggest that the functional status of the thyroid and pituitary glands has not been altered by treatment with FOE 5043 and that reductions in circulating levels of T4 are being mediated indirectly through an increase in the biotransformation and excretion of thyroid hormone in the liver.

Extrathyroidally mediated changes in circulating thyroid hormone concentrations in the male rat following administration of an experimental oxyacetamide (FOE 5043).

Evidence of increased hepatic metabolizing capacity coupled with reductions in serum thyroxine (T4) levels were noted in the rat during preliminary toxicity studies with FOE 5043, an oxyacetamide with herbicidal properties. These findings were consistent with reports in the literature suggesting that declines in T4 as a result of exposure to various classes of chemicals may be mediated extrathyroidally, such as through chemical induction of hepatic thyroid hormone metabolism. To examine this question with respect to FOE 5043, male rats were surgically thyroidectomized and provided thyroid hormone replacement therapy via implanted osmotic minipumps capable of maintaining a T4/triiodothyronine (T3) serum concentration for approximately 4 weeks at a level comparable to that of euthyroid controls. Seven days after minipump implantation, thyroidectomized + T4/T3 (TX + T4/T3) and nonthyroidectomized intact rats (NTX) were fed diets containing 0, 25, 1000, or 3000 ppm FOE 5043 for up to 3 weeks. Dose-related and equivalent declines in total and free serum T4 levels in both TX + T4/T3 and NTX rats were measured at Weeks 1, 2, and 3. Alterations in thyrotropin, total, free, and reverse serum T3 levels were also noted in both TX and NTX animals; however, a compound-related trend was difficult to discern and, when compared to the T4 response, the changes were markedly less consistent with respect to both time and dose. Additionally, dose-related increases in absolute and relative liver weights were measured in both TX + T4/T3 and NTX animals. As the only source of thyroid hormone in the TX + T4/T3 animals was that provided by the pump, these data suggest that FOE 5043-induced alterations in serum thyroid hormone levels, most notably T4, are being mediated indirectly, possibly as a result of increased hepatic metabolism, rather than through a direct effect on the thyroid gland.

Neuromuscular hamartoma (benign "Triton" tumour) in a mouse.

Histological examination of a 22-month-old CD-1 mouse revealed a threefold enlargement of the right trigeminal ganglion. This change was due to the presence of well-differentiated striated muscle fibers intermingling with nerves and ganglion cells. The number of ganglionic Schwann cells was also increased as demonstrated by their positive S-100 protein staining. In addition, slight interstitial mononuclear cell infiltration and fibrosis were observed. The myocytes, which stained positive for myoglobin and desmin, and the proliferated Schwann cells did not show any signs of cellular or nuclear atypia. The lesion was diagnosed as "neuromuscular hamartoma (benign "Triton" tumor)" reflecting the capability of either Schwann cells or neural crest derived precursor cells to differentiate into various other cell types.

Morphological comparison between benign keratinizing cystic squamous cell tumours of the lung and squamous lesions of the skin in rats.

Approximately 700 cases of keratinizing cystic squamous lung lesions in rats were investigated by light microscopy in order to clarify the nomenclature and classification of these lesions. The structure of benign keratinizing cystic squamous cell tumours of the lung was compared to that of cystic squamous lesions in the skin of rats, with consideration of data from the literature. We conclude that the reviewed keratinizing cystic squamous cell lesions of the lung are true neoplasms and that the growth pattern of these cystic lesions is inconsistent with that of a simple cyst. In the development of squamous lung cancer, a continuum of proliferation from exaggerated metaplasia through benign cystic tumours to invasive squamous cell carcinomas can be observed.