Abstract:
:Substantial progress in understanding nongenotoxic or secondary mechanisms of tumorigenesis has been made over the past decade. However, the methods used in regulated studies for assessment of carcinogenic potential in chemicals in development have not evolved significantly. Based on the experience of over 30 yr of testing and the societal need to control costs, reevaluation of standard cancer rodent bioassay protocols is being done. Expert consensus after evaluating the results of full-scale rodent bioassays of both sexes in 2 species is that a reduced protocol is acceptable. After review of relevant data, it is our opinion that cancer hazard assessment in male and female rats only would be sufficient and that, in the future, mouse bioassays will not add significant value on a routine basis. We are unable to find an example of a mouse tumorigenic finding that predicts a confirmed or probable human response with negative findings in a rat bioassay. The savings realized by eliminating mouse testing from routine protocols would be substantial and better spent in expanding short-term studies to add to our understanding of chemical carcinogenesis.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Alden CL,Smith PF,Piper CE,Brej Ldoi
10.1177/019262339602400610subject
Has Abstractpub_date
1996-11-01 00:00:00pages
722-5issue
6eissn
0192-6233issn
1533-1601journal_volume
24pub_type
杂志文章,评审abstract::Livers of male Sprague-Dawley rats were evaluated for foci and nodules 90 days and 16 months after one or two oral doses of 1,2-dibromoethane (DBE). Rats (190 g) were given the following oral treatments. Controls received corn oil (2.5 ml/kg) at 0 and 24 hr. DBE X 1 received corn oil at 0 hr and 75 mg DBE/kg at 24 hr....
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338401200402
更新日期:1984-01-01 00:00:00
abstract::The carcinogenic potential of chloroform was evaluated in a short-term carcinogenicity testing system using CB6F1 rasH2-Tg (rasH2-Tg) mice. Chloroform was administered to rasH2-Tg males at doses of 28, 90, or 140 mg/kg and rasH2-Tg females at 24, 90, or 240 mg/kg by oral gavage for 26 weeks. Wild-type (non-Tg) male an...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230252929909
更新日期:2002-05-01 00:00:00
abstract::Alloxan-induced diabetic rats frequently exhibit proliferative lesions of squamous hyperplasia accompanied by chronic inflammation and Candida albicans infection in the forestomach, and some lesions progress to squamous cell carcinoma (SCC). Candida infection causes not only hyperplastic changes with inflammation but ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309344204
更新日期:2009-10-01 00:00:00
abstract::This study aimed to evaluate the carcinogenic potential of the herbicide Diuron in a two-stage rat medium-term mammary carcinogenesis model initiated by 7,12-dimethylbenz(a)anthracene (DMBA). Female seven-week-old Sprague-Dawley (SD) rats were allocated to six groups: groups G1 to G4 received intragastrically (i.g.) a...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310396904
更新日期:2011-04-01 00:00:00
abstract::Dysfunction of the visual system remains a leading cause of human disability worldwide. Preclinical studies are a key component of efforts to develop drugs and devices to ameliorate visual impairment. Although new opportunities for the delivery of targeted ocular therapeutics have been created, clinical success has be...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320986558
更新日期:2021-01-05 00:00:00
abstract::The clinical, laboratory, and pathologic features of a syndrome in dogs characterized by intermittent pain, fever, neutrophilia, and necrotizing arteritis are described to alert others involved in toxicity testing to the existence of this disorder. It is considered that this idiopathic syndrome is a latent condition, ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338901700109
更新日期:1989-01-01 00:00:00
abstract::Benzene is of particular concern because of recent research indicating that benzene exposure can result in toxicity. The hematotoxic effect of benzene is mentioned. However, there is little knowledge about the correlation between the biomarker of benzene exposure and changes in red blood cell parameters. Here, the cor...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230601156278
更新日期:2007-02-01 00:00:00
abstract::The spleen is the largest secondary lymphoid organ, is considered the draining site for compounds that are administered intravenously, and is therefore considered an important organ to evaluate for treatment-related lesions. Due to the presence of B and T lymphocytes, the immunotoxic effects of xenobiotics or their me...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230600865523
更新日期:2006-01-01 00:00:00
abstract::Many new observations have been made correlating changes in renal morphology with changes in renal function. These changes have led to a better definition of the various segments which make up the renal tubule. These morphological patterns vary in different species as is documented by morphologic studies and by differ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262338601400103
更新日期:1986-01-01 00:00:00
abstract::Partial hepatectomy (PH) and neonatal rat short-term liver focus models were used to examine the effects of selected chemicals that had been previously tested in the National Toxicology Program (NTP) 2-yr carcinogenicity studies. C.I. Solvent Yellow 14, monuron, chlorendic acid, and 4-hydroxyacetanilide were tested fo...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623389017004110
更新日期:1989-01-01 00:00:00
abstract::Single doses of aspirin induce scattered foci of necrosis of proximal tubules in some strains of rats, whereas acute or sub-acute administration of phenylbutazone causes renal papillary necrosis. Initially, using Sprague-Dawley rats of CFY and CD strains, it became clear that these rats were not as susceptible to thes...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400214
更新日期:1986-01-01 00:00:00
abstract::Cysteamine is the first chemical identified that induces acute and chronic duodenal ulcers in rodents. Structure-activity studies with cysteamine, propionitrile and their derivatives, as well as with analogues of toluene, revealed numerous alkyl and aryl duodenal ulcerogens. Among these, one of the most interesting fr...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262338801600213
更新日期:1988-01-01 00:00:00
abstract::In a simulated fire-related smoke exposure protocol, New Zealand white rabbits were utilized to investigate the potential effects of the 21-aminosteroid (lazaroid) analog U75412E on the early events of acute lung injury. Inhalation of a total of 1.6 mg/kg U75412E aerosolized at a rate of 1.53 mg/min at 0.5 hr after sm...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339902700309
更新日期:1999-05-01 00:00:00
abstract::The use of minipigs in preclinical safety testing of pharmaceuticals is considered an alternative to the more traditional dog and nonhuman primate (NHP) nonrodent species. Substantial evidence exists to suggest that the anatomy, physiology, and biochemistry of minipigs are similar enough to humans to consider them as ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623315617562
更新日期:2016-04-01 00:00:00
abstract::The lung is a target organ for the toxic effects of several chemical agents, including natural products, industrial chemicals, pesticides, environmental agents, and occasionally, drugs. Factors that establish the lung as a target organ include selective tissue exposure, high tissue oxygenation, and the presence of bio...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339101900415
更新日期:1991-01-01 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::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::Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inocula...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490524247
更新日期:2004-11-01 00:00:00
abstract::High-resolution digitalizing of histology slides facilitates the development of computational alternatives to manual quantitation of features of interest. We developed a MATLAB-based quantitative histological analysis tool (QuHAnT) for the high-throughput assessment of distinguishable histological features. QuHAnT val...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314544379
更新日期:2015-04-01 00:00:00
abstract::The toxic effects of a mixture of 2-aminoanthracene (2-AA), benzanthracene (BA), and dinitropyrene isomers (DNP), and the toxic effects of these compounds individually, were investigated in the Fischer-344 rat following dietary exposure via a powdered basal diet. Animals were sacrificed at 14-, 30-, and 80-days of die...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262301316905291
更新日期:2001-05-01 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::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::GJA1 gene (Connexin43, also known as Cx43) is the most abundant gap junction protein isoform in animal cells and is associated with bone development in embryos. The objective of the present work was to evaluate in vivo osteal development in GJA1-deficient fetal mice through determination of the histological and molecu...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311422075
更新日期:2011-12-01 00:00:00
abstract::The preclinical safety of RPR 106541, a novel 17-thiosteroid, was evaluated in young adult and mature dogs by inhalation exposure for 26 weeks and 52 weeks, respectively. A dry powder formulation of RPR 106541 in lactose was administered to young adult dogs (approximately 6 months of age at initiation) at doses of 0 (...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262330002800202
更新日期:2000-03-01 00:00:00
abstract::Furan is a potent cholangiocarcinogen in rat by an as yet undefined mechanism. The risk to man remains unclear. Using a time-course stop study design, we have investigated the potential of furan to induce oxidative stress and DNA damage associated with inflammatory and regenerative responses in rat liver. Furan was ad...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623309357946
更新日期:2010-02-01 00:00:00
abstract::The title of the 2016 Society of Toxicologic Pathology (STP) Symposium was the "Basis and Relevance of Variation in Toxicologic Responses." Many factors may contribute to variation in toxicologic responses and can confound results, complicate interpretation of data, interfere with reproducibility, and make extrapolati...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623316675765
更新日期:2017-01-01 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
abstract::The new Appendix A of the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes, which gives guidelines for accommodation and care of animals and was approved on June 15, 2006, was the main reason the authors decided to investigate the origins of the regulatio...
journal_title:Toxicologic pathology
pub_type: 传,历史文章,杂志文章,评审
doi:10.1177/0192623309345871
更新日期:2009-10-01 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::At present (putative) human carcinogens are identified via epidemiological studies and testing using the chronic 2-yr rodent bioassay. Both methods have severe limitations in that they are slow, insensitive, expensive, and are also hampered by many uncertainties. The development of methods to modify specific genes in ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339802600605
更新日期:1998-11-01 00:00:00