Abstract:
:When chemicals that are nongenotoxic in conventional assays produce increases in tumor incidence in rodents in chronic bioassays, the determination of the significance of these data for human safety is a challenging task. An important first step in this process is consideration of available data on the mechanism of action and biological properties of the chemical as well as pharmacokinetic and metabolism data in the species showing the response. In recent years, there has been an increase in the understanding of so-called "secondary mechanisms" of carcinogenesis (e.g., thyroid tumors in rats following exposure to enzyme inducers). Application of these data may assist in determination of human risk. There are 2 important questions that will be explored and developed: Are there biological effects produced in the test species that could explain the increase in tumor incidence, and will these effects be reproduced in humans? What is the exposure to the chemical that is associated with the increase in tumors, and how does this relate to exposure in humans?
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
MacDonald JS,Lankas GR,Morrissey REdoi
10.1177/019262339402200206subject
Has Abstractpub_date
1994-03-01 00:00:00pages
124-40issue
2eissn
0192-6233issn
1533-1601journal_volume
22pub_type
杂志文章,评审abstract::B6.A.D. (Ahr(d)/Nat(s)) mice were utilized to investigate the short-term pulmonary response to JP-8 jet fuel (JP-8) aerosol inhalation. Mice were nose-only exposed to atmospheres of 0 to 118 mg/m3 for 1 h/d over a period of 7 days to further test the hypothesis that JP-8 concentrations below the permissible exposure l...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800504
更新日期:2000-09-01 00:00:00
abstract::Toxicology of the male reproductive system has received increased interest in recent years partly fuelled by the growing reports of falling sperm counts and rising reproductive disorders in the human population. Recently revised regulatory guidelines for the safety assessment of pharmaceuticals and chemicals on reprod...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339702500201
更新日期:1997-03-01 00:00:00
abstract::One application of genomics in drug safety assessment is the identification of biomarkers to predict compound toxicity before it is detected using traditional approaches, such as histopathology. However, many genomic approaches have failed to demonstrate superiority to traditional methods, have not been appropriately ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230500321213
更新日期:2005-01-01 00:00:00
abstract::A retrospective analysis of microscopic evaluation data from control (device and/or saline-treated) animals in intrathecal studies in monkeys, dogs, sheep, and rats was conducted. The studies were performed by multiple testing facilities. All slide preparation and microscopic evaluation were conducted in the laborator...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310391679
更新日期:2011-01-01 00:00:00
abstract::In the present study, susceptibility of CB6F1 mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and p53 gene knockout mice (p53 (+/-) mice) to urethane-induced lung carcinogenesis was compared under the same experimental conditions. Both strains were administered 500 ppm urethane in their drinking water for...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230590908231
更新日期:2005-01-01 00:00:00
abstract::We describe 2 cases of a relatively rare tumor diagnosed as pituicytoma in the pars nervosa of rat pituitary. This tumor was spontaneously noted in one 110-week-old female and one 109-week-old male Fischer 344 (F344)/DuCrj rats during 2-year carcinogenicity studies. Although no gross abnormality of the pituitary was d...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800612
更新日期:2000-11-01 00:00:00
abstract::During preclinical investigations into the safety of drugs and chemicals, many are found to interfere with reproductive function in the female rat. This interference is commonly expressed as a change in normal morphology of the reproductive tract or a disturbance in the duration of particular phases of the estrous cyc...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623308315665
更新日期:2008-04-01 00:00:00
abstract::Specific regions in the rodent larynx exhibit cellular changes in response to inhaled xenobiotics. These regions include the base of the epiglottis, ventral pouch, and medial surfaces of the vocal processes of the arytenoid cartilages. There are interspecies differences among laboratory rodents in the microscopic anat...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100604
更新日期:1993-11-01 00:00:00
abstract::Reticulum cell hyperplasia (RCH) was a term used for many years by the National Toxicology Program (NTP) to describe a certain non-neoplastic bone marrow lesion of rats. Retrospective microscopic evaluation of RCH lesions and immunohistochemistry analyses were performed to reassess and further characterize these lesio...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623319890610
更新日期:2020-02-01 00:00:00
abstract::Complete evaluation of the toxicity of a new chemical entity requires critical analysis of the pattern of positive and negative findings in all types of toxicity tests, pharmacokinetics and metabolism in the species examined, and correlation of the effects with information about its pharmacodynamic and pharmacological...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200216
更新日期:1994-03-01 00:00:00
abstract::The prevalence of liver and skin tumors in brown bullhead ( Ameiurus nebulosus) from the Anacostia River (Washington, DC) and nearby areas was determined in 2014, 2015, and 2016. The objectives were to (1) compare tumor prevalence across space and time; (2) analyze the 1992-2016 Chesapeake Bay Tumor Database to identi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623318823150
更新日期:2019-02-01 00:00:00
abstract::ZD7114, [(S)-4-[2-(2-hydroxy-3 phenoxypropylamine)ethoxy]-N-(2-methoxyethyl) phenoxyacetamide], and ZD2079, [(R)-N-(2-[4- (carboxymethyl)phenoxy]ethyl)-N-(beta-hydroxyphenethyl)ammonium chloride], are beta 3-adrenoceptor stimulants with selectivity for brown adipose tissue. ZD7144 is the hydrochloride salt of the S-en...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339902700203
更新日期:1999-03-01 00:00:00
abstract::Aminoglycoside antibiotics are ototoxic in mammals and birds, including recently hatched chicks, but chicken embryos are insensitive to the ototoxicity of gentamicin, kanamycin, and streptomycin. To determine whether or not the insensitivity is due to a lack of antibiotic distribution to the avian cochlea, the distrib...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200103
更新日期:1994-01-01 00:00:00
abstract::Liver resection is a suitable option for the treatment of certain hepatic conditions, particularly hepatocarcinomas, in patients with cirrhosis. However, this disease impairs liver regeneration, which increases the risk of liver failure and postoperative death. Supportive treatments for regeneration of the remaining l...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313486316
更新日期:2014-01-01 00:00:00
abstract::Carcinogenicity testing of antitumor agents in animal bioassays has been proposed because of the potential for carcinogenicity of this class of agents and the expectation that such testing may indicate prospectively the target organs of any related human oncogenesis. The literature reveals the anticipated confirmation...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338501300305
更新日期:1985-01-01 00:00:00
abstract::Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utilized hemicastration and electron microsc...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600932455
更新日期:2006-01-01 00:00:00
abstract::Gadolinium is used as a contrast media for magnetic resonance imaging and, experimentally, to block Kupffer cell phagocytosis. In this study, we utilize electron probe microanalysis to determine the subcellular localization of gadolinium chloride (GdCl3) administered to mice in a short-term toxicology study. Male CD-1...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339602400508
更新日期:1996-09-01 00:00:00
abstract::Astrocytes assume multiple roles in maintaining an optimally suited milieu for neuronal function. Select astrocytic functions include the maintenance of redox potential, the production of trophic factors, the regulation of neurotransmitter and ion concentrations, and the removal of toxins and debris from the cerebrosp...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623310385254
更新日期:2011-01-01 00:00:00
abstract::The spleen contains hematopoietic and lymphoid elements, is a primary site of extramedullary hematopoiesis, and removes degenerate and aged red blood cells as well as particulate materials and circulating bacteria from the blood supply. Lesions of this important component of the immune system may center on the red pul...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600867750
更新日期:2006-01-01 00:00:00
abstract::Some developmental dual-acting PPARalpha/gamma agonists, such as ragaglitazar, have shown carcinogenic effects in the rodent urinary bladder urothelium after months-years of dosing. We examined early (precancerous) changes in the bladder urothelium of rats orally dosed with ragaglitazar, using a newly developed flow c...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230500214657
更新日期:2005-01-01 00:00:00
abstract::This report describes the findings of preclinical testing of SCH 351591, a selective phosphodiesterase 4 inhibitor, in CD-1 mice over a wide range of doses, in which the heart and reproductive organs of both sexes demonstrated toxic effects. Repeat-dose toxicity studies assessed 5, 15, 50, 100, 200, 400, and 800 mg/kg...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310370463
更新日期:2010-06-01 00:00:00
abstract::The 2019 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Raleigh, North Carolina, at the Society of Toxicologic Pathology's 38th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This ar...
journal_title:Toxicologic pathology
pub_type:
doi:10.1177/0192623319876929
更新日期:2019-12-01 00:00:00
abstract::In non-rodent toxicity studies supporting pharmaceutical or chemical product registration, the value of histopathology evaluation of all tissues from all animals from all dose groups is an ongoing discussion topic among pathologists. This manuscript documents an examination of this topic through a retrospective review...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623312439642
更新日期:2012-07-01 00:00:00
abstract::Kozlowski, C., Brumm, J., and Cain, G. (2018). An Automated Image Analysis Method to Quantify Veterinary Bone Marrow Cellularity on H&E Sections. Tox Path46, 324-335. (Original DOI: 10.1177/0192623318766457). Kozlowski, C., Fullerton, A., Cain, G., Katavolos, P., Bravo, J., and Tarrant, J. M. (2018). Proof of Concept ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,已发布勘误
doi:10.1177/0192623318794946
更新日期:2018-08-01 00:00:00
abstract::Environmental pollutants, chemicals, and drugs have an impact on children's immune system development. Mexico City (MC) children exposed to significant concentrations of air pollutants exhibit chronic respiratory inflammation, systemic inflammation, neuroinflammation, and cognitive deficits. We tested the hypothesis t...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623308329340
更新日期:2009-02-01 00:00:00
abstract::Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to deter...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623312464122
更新日期:2013-01-01 00:00:00
abstract::The role of articular chondrocytes and matrix degrading enzymes such as collagenase and neutral protease in the pathogenesis of quinolone-induced cartilage degeneration was investigated in immature guinea pigs. Articular cartilage from nalidixic acid (NA) treated guinea pigs was examined for the presence of protease a...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339001800209
更新日期:1990-01-01 00:00:00
abstract::Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490261348
更新日期:2004-01-01 00:00:00
abstract::Phosphatidylinositol 3-kinases (PI3Ks) regulate intracellular signaling events for multiple cell surface receptors. Phosphatidylinositol 3-kinase δ, 1 of 4 class I PI3K isoforms, is primarily found in leukocytes and regulates immune cell functions. Here, we report changes in the immune and digestive systems that were ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320966238
更新日期:2020-12-01 00:00:00
abstract::Two-year toxicity studies were conducted on the widely used herbal products, goldenseal and milk thistle, in male and female F344/N rats and B6C3F1 mice. With goldenseal root powder, the primary finding was an increase in liver tumors in rats and mice, and with milk thistle extract, a decrease in spontaneous backgroun...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310394211
更新日期:2011-02-01 00:00:00