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PubMed1980

Death from inhalant abuse: toxicological and pathological evaluation of 34 cases.

Thirty-four cases of death related to the deliberate inhalation of various solvents or gases were studied regarding the toxicology and pathology of this phenomenon. A method was developed for detection of these agents in blood and other autopsy specimens, utilizing flame ionization gas chromatography. The detection in the blood of components of the products inhaled usually confirmed the recent use of the substances. Death was usually sudden, occurring during or shortly after use of the inhalants, and was consistent with the development of cardiac arrhythmias. Of the cases available for histological evaluation, liver damage was apparent in some cases.

Adolescent↗
PubMed1988

Clinical, clinicopathologic, pathologic, and toxicologic alterations associated with gossypol toxicosis in feeder lambs.

The toxicity of gossypol was studied in 20, 8-week-old feeder lambs that weighed approximately 16 kg. The lambs were allotted to 4 groups (A, B, C, D) and given (orally for 30 days) a daily dosage of gossypol (0, 45, 136, or 409 mg, respectively). Lambs were observed twice daily until they died or were euthanatized on the day the last dose was given. Clinical, electrocardiographic, clinicopathologic, pathologic, and toxicologic findings were recorded. All lambs given 409 mg of gossypol (group D) died before the end of the 30-day study. In this group, clinical signs included sudden death and/or chronic dyspnea syndromes. One group-B lamb had chronic dyspnea, but did not die. Electrocardiographic abnormalities observed in gossypol-treated lambs included increased amplitude of the T wave and decreased duration of the ST segment. Clinicopathologic alterations in group-D lambs included high serum total lactate dehydrogenase and lactate dehydrogenase liver-specific isoenzyme activities. Serum total creatine kinase activity decreased markedly in lambs of all groups treated with gossypol. Hemoglobinuria was detected in 2 group-D lambs. The average daily weight gain was remarkably consistent in lambs of all groups, except in 1 lamb each of groups D and B. Lambs were necropsied when they died or on day 30 of the study. The heart of gossypol-treated lambs weighted more than did that of untreated (control group A) lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMedDate not supplied

Magnetic resonance microscopy--a new tool for the toxicologic pathologist.

Parallel to its many applications in medical imaging, magnetic resonance (MR) microscopy is a potentially powerful tool in toxicologic pathology. Because of the intrinsic qualities of MR microscopy (noninvasiveness, 3-dimensionality, and slicing in any chosen plane), the scientist has a new means by which to investigate different types of lesions based on differential contrast. By choosing appropriate proton stains to probe the state of the water in tissues, organ structure and vasculature can be seen and progressive lesion development can be followed in a given animal. This paper discusses toxicologic pathology applications for MR microscopy and compares MR microscopy with conventional histopathology using a time-course study of bromobenzene-induced hepatotoxicity in rats. Hematoxylin and eosin (H&E)-stained histological sections are compared with MR microscopy images from fixed tissue blocks to demonstrate one of the applications of MR microscopy to toxicologic pathology. The results indicate that MR microscopy is as sensitive as conventional H&E staining in detecting bromobenzene-induced hepatic lesions.

Animals↗
PubMedDate not supplied

Diagnostic criteria for degenerative, inflammatory, proliferative nonneoplastic and neoplastic liver lesions in medaka (Oryzias latipes): consensus of a National Toxicology Program Pathology Working Group.

Diagnostic criteria are presented for degenerative, inflammatory, nonneoplastic proliferative, and neoplastic lesions in the liver of medaka (Oryzias latipes), a small fish species frequently used in carcinogenesis studies. The criteria are the consensus of a Pathology Working Group (PWG) convened by the National Toxicology Program. The material examined by the PWG was from Medaka exposed to N-nitrosodiethylamine for 28 days, removed to clean water, and sacrificed 4, 6, or 9 mo after initiation of exposure. Degenerative lesions included hepatocellular intracytoplasmic vacuolation, hepatocellular necrosis, spongiosis hepatis, hepatic cysts, and hepatocellular hyalinization. Inflammatory lesions consisted of granulomas, chronic inflammation, macrophage aggregates, and focal lymphocytic infiltration. Nonneoplastic proliferative lesions comprised foci of cellular alteration (basophilic focus, eosinophilic focus, vacuolated focus, and clear cell focus) and bile duct hyperplasia. Neoplastic lesions included hepatocellular adenoma, hepatocellular carcinoma, cholangioma, and cholangiocarcinoma. Two lesions composed mainly of spindle cells were noted, hemangiopericytoma and spindle cell proliferation. Rather than being an exhaustive treatment of medaka liver lesions, this report draws from the published literature on carcinogen-induced liver lesions in medaka and other fish species and attempts to consolidate lesion criteria into a simplified scheme that might be useful to pathologists and other researchers using medaka lesions for risk assessment or regulatory purposes.

Adenoma↗
PubMed2005

Trouble shooting in toxicopathology.

Toxicopathology, also referred to as toxicologic pathology, can be defined as the study of structural and functional changes in cells, tissues, and organs that are induced by toxicants (such as drugs, industrial and agricultural chemicals), toxins (chemicals of biological origin such as mycotoxins and phycotoxins), and physical agents (such as heat and radiation); the investigation of the mechanisms by which these changes are induced; and the development of risk assessment and risk management policies based on such information. Toxicologic pathology primarily deals with the morphologic or structural effects of the toxicant and the mechanism by which this structural effect is induced. This article highlights some of the problems that toxicologic pathologists may encounter in obtaining and interpreting pathology lesions. By alerting toxicologists to some of these issues, it is hoped that a better understanding of the use and limitations of toxicologic pathology data will occur.

Animals↗
PubMed1994

A 13-week toxicologic and pathologic evaluation of prolonged cytochromes P450 inhibition by 1-aminobenzotriazole in male rats.

The pharmacologic, toxicologic, and microscopic effects of 100 mg/kg/day of 1-Aminobenzotriazole (ABT), a suicide substrate inhibitor of cytochromes P450, were assessed in male Sprague-Dawley rats over a 13-week period. Hepatic cytochromes P450 levels and resorufin dealkylase activity were decreased to less than 30% of control values beginning at Day 2 and from Day 8 to Day 92. These decreases were not accompanied by overt clinical toxicity, e.g., changes in body weight, food consumption, or clinical appearance, during the study. Hemoglobin, hematocrit, and erythrocyte counts were slightly decreased at 8, 29, and 92 days and were accompanied by increased spleen weights and extramedullary hematopoiesis. Additionally, mean corpuscular hemoglobin concentration, mean corpuscular volume, red cell distribution width, and mean corpuscular hemoglobin were slightly increased at 92 days. Increases in liver weights at 8, 29, and 92 days were accompanied by centrilobular hypertrophy and intracytoplasmic vacuolization consistent with lipid accumulation. Thyroid stimulating hormone (TSH) was slightly elevated and triiodothyronine and thyroxine were slightly decreased at 29 days. TSH was also slightly elevated at 8 and 92 days, and thyroid gland weights were increased at 8, 29, and 92 days with microscopic evidence of hyperplasia and hypertrophy of thyroid gland follicular cells. Increased adrenal weights and hypertrophy of the zona fascicularis of the adrenal gland were observed at 8, 29, and 92 days. Kidney weights were also increased at these assessments. Changes in the thyroid gland, the thyroid hormone profile, and the liver may reflect increased synthesis of microsomal enzymes, an effect that is sometimes difficult to demonstrate directly with suicide substrate inhibitors of cytochromes P450. In general, the effects of daily ABT administration to male rats at a dose that significantly reduces oxidative metabolism over a 13-week period were considered to be well-tolerated under controlled laboratory conditions.

Animals↗
PubMedDate not supplied

Clinical, pathologic, and toxicologic findings in asthma deaths in Cook County, Illinois.

To identify factors contributing to asthma mortality and improve our understanding of airway pathology in fatal asthma, we studied 44 cases of fatal asthma using records of one pathologist in the Office of the Medical Examiner. Records included death certificates, autopsies, toxicology, accounts by family and friends of the terminal episode, medical history of the deceased, police and paramedic reports, and hospital charts. Additionally, we interviewed by telephone surviving family and friends. Six (17%) of 35 patients were using inhaled corticosteroids at time of death. Of the nine patients who had seen a physician within 2 weeks of death, two were using corticosteroids. Toxicology was positive in 16 (38%) of 42 cases. Of the 20 patients with sudden-onset asthma (prodrome of increasing symptoms < 1 hour before death), 9 (45%) had positive toxicology. Patients with both sudden-onset and slow-onset asthma (prodrome > 3 hours before death) had airway mucosal or submucosal eosinophilic or neutrophilic infiltrates or both, as well as airways with and without mucus plugging. These findings indicate that asthma deaths are confounded by substance abuse and lack of anti-inflammatory therapy, and there is a heterogeneity in histological findings in sudden-onset and slow-onset asthma.

Adolescent↗
PubMed1993

Toxicological and pathological applications of proliferating cell nuclear antigen (PCNA), a novel endogenous marker for cell proliferation.

A major stimulus to study cell proliferation, particularly in rodent carcinogenicity assays and human tumors, has been the belief that the quantification of this fundamental biological process will provide the toxicologist and pathologist with objective data allowing a better understanding of the mechanisms involved in the toxicity and/or carcinogenicity of certain compounds as well as guiding more effective management of patients afflicted with neoplasia. Among the markers used for cell proliferation measurement, PCNA has recently gained much attention and holds much promise as it is intricately involved in the cell replication processes. It not only could allow measurement of the replication rates without necessitating pretreatment of the animal/tissue in prospective studies, but also would allow retrospective assessment of the proliferative rates in archival tissues due to the conservation of this marker in fixed and paraffin-embedded tissues. Finally, knowledge of the function of PCNA in the cell cycle and its regulation by other factors may help us understand the advantages and limitations of PCNA as a cell proliferation marker in its application in toxicology and as a prognostic marker in human tumors.

Animals↗
PubMedDate not supplied

Spontaneous and chemically induced proliferative lesions in Tg.AC transgenic and p53-heterozygous mice.

Recently, the use of selected genetically altered mouse models in the detection of carcinogens after short-term chemical exposures has been evaluated. Studies of several chemicals conducted by the National Toxicology Program in Tg.AC transgenic and heterozygous p53-deficient mice have been completed recently and represent a major contribution to this effort, as well as the largest accumulation to date of toxicologic pathology data in these 2 lines of mice. The purpose of this report is to describe the proliferative target organ effects observed in this set of studies, as well as to present the tumor profile in the control groups of this data set. These findings provide a comprehensive toxicologic assessment of these 2 genetically altered mouse strains, which are of emerging importance in toxicologic pathology.

Animals↗
PubMed1988

Pathological and toxicological studies of calves fed a high concentration cotton seed meal diet.

Feeding a high concentration of cotton seed meal to young calves resulted in death with lesions compatible with gossypol toxicity. Calves were fed two different commercially prepared rations. Free gossypol concentrations in different lots of the 17% protein ration varied from 250 to 380 ppm, and the 13% protein ration varied from 40 to 240 ppm. Serum sorbitol dehydrogenase elevation was the most consistent clinical pathological finding. The mean serum sorbitol dehydrogenase concentrations for moribund, hospitalized, and clinically healthy calves were 277, 34, and 45 units/liter. The mean for sorbitol dehydrogenase concentration for healthy calves not fed cotton seed meal was 18 units/liter. Gross lesions included severe effusion of a high protein content fluid into the body cavities of most calves, edema of the mesentery, and hepatomegaly. The most consistent histological lesion was severe centrilobular hepatic necrosis. Elevated levels of liver gossypol were demonstrated. The mean liver gossypol concentration for three calves was 41.7 micrograms/g on a wet weight basis.

Animal Feed↗