Evaluation of clinical pathology data: correlating changes with other study data.

Abstract:

:During the conduct of in vivo toxicology studies, in-life, clinical pathology, and anatomic pathology parameters are collected and interpreted. These sets of parameters are evaluated in an integrative manner to determine the overall toxicity of a test article. For clinical pathology parameters, the inherent variability and physiologic factors affecting each analyte must be understood prior to interpretation. Changes in clinical pathology parameters that are considered to be test article-related are then assessed with respect to changes in the concurrent data sets such as clinical signs and anatomic pathology to determine the underlying pathophysiology. In this article, examples of hemolysis and hepatotoxicity are used to demonstrate the relationships among the various parameters and data sets. Whereas there was tight correlation of all data sets in the example of hemolysis in rats, the examples of altered enzymes and other biomarkers indicating liver injury and dysfunction were more often discordant with other data sets.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Everds NE

doi

10.1177/0192623314555340

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

90-7

issue

1

eissn

0192-6233

issn

1533-1601

pii

0192623314555340

journal_volume

43

pub_type

杂志文章
  • Two-year evaluation of misoprostol for carcinogenicity in CD Sprague-Dawley rats.

    abstract::The carcinogenic potential of misoprostol, a synthetic prostaglandin E1 analogue with anti-ulcer potential, was evaluated in CD Sprague-Dawley rats. The compound was given daily by gavage at 24, 240, and 2,400 micrograms/kg, up to 150 times the daily human dose for 2 years. Necropsies were done on all animals and the ...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262338701500201

    authors: Dodd DC,Port CD,Deslex P,Regnier B,Sanders P,Indacochea-Redmond N

    更新日期:1987-01-01 00:00:00

  • Emanuel Edward Klein--the father of British microbiology and the case of the animal vivisection controversy of 1875.

    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

    authors: Atalić B,Fatović-Ferencić S

    更新日期:2009-10-01 00:00:00

  • TCDD: an environmental immunotoxicant reveals a novel pathway of immunoregulation--a 30-year odyssey.

    abstract::I was honored to be the keynote speaker at the 30th Annual Society of Toxicologic Pathology Symposium "Toxicologic Pathology and the Immune System." I had the opportunity to reminisce about events in the 1970s that set the stage for the birth and subsequent growth of the field of immunotoxicology and to summarize my r...

    journal_title:Toxicologic pathology

    pub_type: 历史文章

    doi:10.1177/0192623311427710

    authors: Kerkvliet NI

    更新日期:2012-01-01 00:00:00

  • Development of a computational high-throughput tool for the quantitative examination of dose-dependent histological features.

    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

    authors: Nault R,Colbry D,Brandenberger C,Harkema JR,Zacharewski TR

    更新日期:2015-04-01 00:00:00

  • The Use of Minipigs for Preclinical Safety Assessment by the Pharmaceutical Industry: Results of an IQ DruSafe Minipig Survey.

    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

    authors: Colleton C,Brewster D,Chester A,Clarke DO,Heining P,Olaharski A,Graziano M

    更新日期:2016-04-01 00:00:00

  • A Brief Overview of the STP 36th Annual Symposium: Musculoskeletal System.

    abstract::The title of the 2017 Society of Toxicologic Pathology symposium was "Musculoskeletal System." A brief overview of the General Scientific Symposium is presented herein and describes the topics presented by each speaker. Symposium speakers addressed subjects pertinent to musculoskeletal system toxicologic pathology and...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/0192623317738211

    authors: Gropp KE,Boyle MC

    更新日期:2017-10-01 00:00:00

  • Early alterations of lung injury following acute smoke exposure and 21-aminosteroid treatment.

    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

    authors: Wang S,Lantz RC,Robledo RF,Breceda V,Hays AM,Witten ML

    更新日期:1999-05-01 00:00:00

  • Histology Atlas of the Developing Mouse Hepatobiliary Hemolymphatic Vascular System with Emphasis on Embryonic Days 11.5-18.5 and Early Postnatal Development.

    abstract::A critical event in embryo development is the proper formation of the vascular system, of which the hepatobiliary system plays a pivotal role. This has led researchers to use transgenic mice to identify the critical steps involved in developmental disorders associated with the hepatobiliary vascular system. Vascular d...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623316630836

    authors: Swartley OM,Foley JF,Livingston DP 3rd,Cullen JM,Elmore SA

    更新日期:2016-07-01 00:00:00

  • Polyomavirus-associated Prostatitis in Wistar Han Rats Following Immunosuppression in a Chronic Toxicity Study.

    abstract::Chronic prostatitis characterized on light microscopic examination by moderate, multifocal, predominantly lymphocytic inflammation associated with epithelial atypia and intranuclear and cytoplasmic inclusion-like material was identified in the prostate gland of 2 Wistar Han rats administered an immunomodulatory test a...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623317713320

    authors: Masek-Hammerman K,Brown TP,Bobrowski WF,Tomlinson L,Debrue M,Whiteley L,Radi Z

    更新日期:2017-07-01 00:00:00

  • Toxicokinetics/toxicodynamic correlations: goals, methods, and limitations.

    abstract::Toxicokinetic (TK) studies are the basis for demonstrating dose-related drug exposure in animals and for ensuring that drug exposure is substantially greater in animals than that expected in humans at therapeutic doses. The usefulness of TK studies can be further enhanced by correlating TK parameters with relevant tox...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/019262339502300209

    authors: Batra VK

    更新日期:1995-03-01 00:00:00

  • Evaluation of testicular toxicity in safety evaluation studies: the appropriate use of spermatogenic staging.

    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

    authors: Creasy DM

    更新日期:1997-03-01 00:00:00

  • Dermal carcinogenicity in transgenic mice: effect of vehicle on responsiveness of hemizygous Tg.AC mice to phorbol 12-myristate 13-acetate (TPA).

    abstract::The Tg.AC mouse is being evaluated for use in short-term carcinogenicity bioassays. Because the dermal test protocol necessitates dissolving test agents we determined the effects of several solvents on responsiveness of hemizygous mice to dermal applications of the classical skin tumor promoter. phorbol 12-myristate 1...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/019262301317226339

    authors: Stoll RE,Furst SM,Stoltz JH,Lilly PD,Mennear JH

    更新日期:2001-09-01 00:00:00

  • A review of the hepatic tumors related to mixed-function oxidase induction in the mouse.

    abstract::Mixed-function oxidase (MFO) induction in the mouse liver results in a rapid and sustained centrilobular hypertrophy associated with a hyperplastic response. In many studies, the long-term sequela of prolonged exposure is an increased incidence of lesions considered to be adenomas. Studies have shown in aged control m...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/019262339602400411

    authors: Butler WH

    更新日期:1996-07-01 00:00:00

  • The candidate neuroprotective agent artemin induces autonomic neural dysplasia without preventing peripheral nerve dysfunction.

    abstract::Artemin (ART) signals through the GFR alpha-3/RET receptor complex to support sympathetic neuron development. Here we show that ART also influences autonomic elements in adrenal medulla and enteric and pelvic ganglia. Transgenic mice over-expressing Art throughout development exhibited systemic autonomic neural lesion...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230490431475

    authors: Bolon B,Jing S,Asuncion F,Scully S,Pisegna M,Van GY,Hu Z,Yu YB,Min H,Wild K,Rosenfeld RD,Tarpley J,Carnahan J,Duryea D,Hill D,Kaufman S,Yan XQ,Juan T,Christensen K,McCabe J,Simonet WS

    更新日期:2004-05-01 00:00:00

  • Summary of panel discussion: past, present and future of toxicologic pathologists and the contributions to hazard identification and molecular mechanisms of action.

    abstract::One of the major roles for the toxicologic pathologists now and into the future will be to determine the biologic significance of chemically induced biochemical and molecular alterations detected in whole tissue homogenates or cell cultures. The biologically significant effects will then require further analysis to de...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/019262301301418973

    authors: Miller RT,Davis BJ

    更新日期:2001-01-01 00:00:00

  • Dose-dependent renal tubular toxicity of harman and norharman in male F344 rats.

    abstract::The renal toxicity of harman and norharman, administered for 2 or 4 weeks at dietary levels of 1,000, 500, or 0 parts per million (ppm), was investigated in 6-week-old male F344/DuCrj rats. Although rats fed 1,000 ppm harman or norharman, but not the 500 ppm level, demonstrated marked body weight retardation from 1 we...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339202000206

    authors: Hagiwara A,Asakawa E,Kurata Y,Sano M,Hirose M,Ito N

    更新日期:1992-01-01 00:00:00

  • Myocardial and reproductive system toxicity of SCH 351591, a selective phosphodiesterase-4 inhibitor, in CD-1 mice.

    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

    authors: Losco PE,Poulet FM,Kaminska-McNamara GZ,Klein MF

    更新日期:2010-06-01 00:00:00

  • The immunopharmacology of immunotoxicology, and immunorestoration.

    abstract::The first part of this paper focuses on the secondary immunodeficiencies caused by immunosuppressive drugs and environmental chemicals. The mechanism of action and the therapeutic effects of azathioprine, glucocorticosteroids, cyclophosphamide, cyclosporin A, and anticancer drugs will be discussed. The immunotoxic act...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/019262338701500310

    authors: Caspritz G,Hadden J

    更新日期:1987-01-01 00:00:00

  • Evaluation of direct and indirect effects of the PPARγ agonist troglitazone on mouse endothelial cell proliferation.

    abstract::Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and PPARγ/α dual agonists are used in the treatment of type 2 diabetes mellitus and hyperlipidemias. In carcinogenicity studies, some of these agonists induced hemangiomas/hemangiosarcomas in mice, but not in rats. We hypothesized that increased endothe...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623311422080

    authors: Kakiuchi-Kiyota S,Arnold LL,Yokohira M,Koza-Taylor P,Suzuki S,Varney M,Pennington KL,Cohen SM

    更新日期:2011-12-01 00:00:00

  • Brief Synopsis: Review of Renal Tubule and Interstitial Anatomy and Physiology and Renal INHAND, SEND, and DIKI Nomenclature.

    abstract::This article provides a synopsis of the first two presentations from the second scientific session of the 37th Annual Symposium of the Society of Toxicologic Pathology in Indianapolis, Indiana, on June 18, 2018; the session focused on acute kidney injury. The first presentation, given by Dr. Kevin McDorman, focused on...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审

    doi:10.1177/0192623318798758

    authors: Crabbs TA,McDorman KS

    更新日期:2018-12-01 00:00:00

  • Spontaneous tumor incidence in rasH2 mice: review of internal data and published literature.

    abstract::Alternate transgenic mouse models are accepted as replacements for the standard carcinogenicity mouse bioassay by regulatory agencies with a companion 2-year rat bioassay. The slower rate of industry acceptance of these shorter transgenic mouse cancer bioassays has been due to lack of historical data and diagnostic cr...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623311436181

    authors: Nambiar PR,Turnquist SE,Morton D

    更新日期:2012-06-01 00:00:00

  • Mission Accomplished: The ACVP/STP Coalition for Veterinary Pathology Fellows Completes Its Objectives, but Its Legacy and Spirit Live On.

    abstract::After 15 years of existence, the ACVP/STP Coalition for Veterinary Pathology Fellows will dissolve, primarily due to lack of renewed financial sponsorship. While in operation, the Coalition organized 32 new training position for veterinary pathologists, supported by $7.4 M from sponsors, including pharmaceutical and b...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623320917970

    authors: Adler R,Clark E,Cline M,Conner M,Crabbs T,Fossey S,Malarkey D,Meseck E,Vernau W,Tornquist S,McDorman K,Rees S,Cockerell G

    更新日期:2020-06-01 00:00:00

  • Pulmonary fibrosis and ferruginous bodies associated with exposure to synthetic fibers.

    abstract::Exposure to synthetic fibers with employment in textile mills can be associated with an elevated risk of interstitial lung disease (ILD). A mechanism of injury has not been determined. ILD can follow exposures to inorganic fibers (e.g., asbestos) which are associated with a mobilization of iron and catalysis of an oxi...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230600932448

    authors: Ghio AJ,Funkhouser W,Pugh CB,Winters S,Stonehuerner JG,Mahar AM,Roggli VL

    更新日期:2006-01-01 00:00:00

  • Three-dimensional mapping of ozone-induced injury in the nasal airways of monkeys using magnetic resonance imaging and morphometric techniques.

    abstract::Age-related changes in gross and microscopic structure of the nasal cavity may alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techn...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,多中心研究

    doi:10.1080/01926230601072343

    authors: Carey SA,Minard KR,Trease LL,Wagner JG,Garcia GJ,Ballinger CA,Kimbell JS,Plopper CG,Corley RA,Postlethwait EM,Harkema JR,Einstein DR

    更新日期:2007-01-01 00:00:00

  • Light microscopic sciatic nerve changes in control beagle dogs from toxicity studies.

    abstract::Although the dog is a common choice among nonrodent species in evaluation of compound safety for regulatory submission, information regarding the incidence of spontaneous or incidental microscopic changes in canine peripheral nerve is limited. A retrospective examination was performed of routine histologic preparation...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623311413786

    authors: Whitney KM,Schwartz Sterman AJ,O'Connor J,Foley GL,Garman RH

    更新日期:2011-08-01 00:00:00

  • Gene expression studies reveal that DNA damage, vascular perturbation, and inflammation contribute to the pathogenesis of carbonyl sulfide neurotoxicity.

    abstract::Carbonyl sulfide (COS) is an odorless gas that produces highly reproducible lesions in the central nervous system. In the present study, the time course for the development of the neurotoxicological lesions was defined and the gene expression changes occurring in the posterior colliculus upon exposure to COS were char...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623309335631

    authors: Morrison JP,Ton TV,Collins JB,Switzer RC,Little PB,Morgan DL,Sills RC

    更新日期:2009-06-01 00:00:00

  • Background Pathological Changes in Minipigs: A Comparison of the Incidence and Nature among Different Breeds and Populations of Minipigs.

    abstract::Swine, especially the miniature swine or minipigs, are increasingly being used in preclinical safety assessment of small molecules, biopharmaceutical agents, and medical devices as an alternate nonrodent species. Although swine have been used extensively in biomedical research, there is a paucity of information in the...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/0192623315611762

    authors: Helke KL,Nelson KN,Sargeant AM,Jacob B,McKeag S,Haruna J,Vemireddi V,Greeley M,Brocksmith D,Navratil N,Stricker-Krongrad A,Hollinger C

    更新日期:2016-04-01 00:00:00

  • A fast histochemical staining method to identify hyaline droplets in the rat kidney.

    abstract::Hyaline droplet formation in the proximal tubular cells of the kidney commonly occurs under different pathological conditions in experimental animals. In rats, intracytoplasmic hyaline droplet formation is predominantly associated with accumulation of the male rat-specific alpha(2u)-globulin, whereas under other (path...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1080/01926230390213775

    authors: de Rijk EP,Ravesloot WT,Wijnands Y,van Esch E

    更新日期:2003-07-01 00:00:00

  • Effect of alternate-day hydrocortisone therapy on the immunologically immature rat. II: Changes in T- and B-cell areas in spleen.

    abstract::The histologic effect of 400 mg/M2/day of hydrocortisone, given alternatively from day 7 to day 19 after birth, was studied on the spleen of the immunologically immature rat. Two days after the cessation of treatment, the periarteriolar lymphatic sheaths were found to be largely depleted of small lymphocytes. Immunope...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章

    doi:10.1177/019262339302100406

    authors: el Fouhil AF,Iskander FA,Turkall RM

    更新日期:1993-01-01 00:00:00

  • Delayed osteoblastic differentiation and bone development in Cx43 knockout mice.

    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

    authors: Chaible LM,Sanches DS,Cogliati B,Mennecier G,Dagli ML

    更新日期:2011-12-01 00:00:00