Biomarkers in Toxicology.

Format:

Book

Author/Creator:

Gupta, Ramesh C.

Language:

English

Subjects (All):

Toxicology.

Physical Description:

1 online resource (1149 pages)

Edition:

1st ed.

Place of Publication:

San Diego : Elsevier Science & Technology, 2014.

Contents:

Front Cover

Biomarkers in Toxicology

Copyright Page

Contents

Foreword

List of Contributors

I: General

1 Introduction

2 Rodents model for toxicity testing and biomarkers

Introduction

The rat

Use in toxicological research

Characteristics

Strain differences

Normal physiological values

Study designs

Routes of test article administration

Oral routes

Dietary vs. gavage methods

Dietary method

Gavage method

Test article preparation

Equipment

Technique

Neonatal administration

Capsule

Water

Intravenous route

Lateral tail vein

Bolus injection

Tail vein infusions

Jugular vein

Infusion

Saphenous, lateral marginal, and metatarsal veins

Dorsal penis vein

Sublingual vein

Intraperitoneal route

Intramuscular route

Subcutaneous route

Topical route

Rectal route

Intranasal route

Inhalation route

Intratracheal administration

End point measurement techniques

Observations and physical examinations

Neurobehavioral examination

Functional observational battery

Locomotor activity

Cardiovascular parameters

Electrocardiography

Recording methods

ECG waveform

Heart rate

Blood pressure

Indirect measurement

Tail Cuff Method

Hindpaw Method

Direct measurement

Blood collection techniques

Retro-orbital plexus

Tail

Tail clip

Venipuncture

Arterial puncture

Cardiac puncture

Abdominal aorta and vena cava

Proximal saphenous and metatarsal vein

Proximal saphenous vein

Metatarsal vein

Decapitation

Cannulation

Inferior vena cava

Abdominal aorta

Subcutaneous ports

Urine collection

Necropsy

Summary

The mouse

Species differences.

Strain differences

Acute toxicity studies

Short-term toxicity studies

Chronic toxicity studies (26 weeks to 2 years)

Carcinogenicity studies (18-24 months)

Teratology studies

Segment II teratology studies

Genetic toxicity studies

Mouse micronucleus assay

Heritable translocation assay

Microbial host-mediated assay

Special studies

Mouse ear swelling test

Dermal carcinogenicity (skin painting) study

Routes of test substance administration

Oral administration

Gavage

Description of technique

Dietary admixtures

Drinking water

Intravenous injection

Intraperitoneal injection

Intramuscular injection

Subcutaneous injection

Intradermal injection

Topical administration

Inhalation

Chamber (whole body)

Head/nose exposure (head only/nose only)

Endpoint data collection

Clinical observations and physical examinations

Clinical laboratory evaluations

Postmortem procedures

The hamster

Species

Syrian hamster

Chinese hamster

European hamster

Armenian hamster

Turkish hamster

Rumanian hamster

Djungarian hamster

South African hamster

Spontaneous tumors

Animal identification

Dosing procedures

Subcutaneous administration

Intradermal administration

Intramuscular administration

Intraperitoneal administration

Intravenous administration

Retro-orbital method

Tail clipping method

Femoral vein method

Jugular vein method

Saphenous vein

Physical parameters

Neonatal body weights.

Body weights and weight gains

Dentition

Life spans

Sexual maturity

Respiratory rate and oxygen consumption

ECG patterns

Clinical laboratory

Glucose

Lipids

Urea nitrogen

Enzymes

Alkaline phosphatase

Alanine aminotransferase

Aspartate aminotransferase

Creatine kinase and lactic dehydrogenase

Thyroid hormones

Reproductive hormones

Adrenal hormones

Proteins

Hematology values

Erythrocytes

Leukocytes

Coagulation

Trypanosomes

Blood gases and pH

Urine values

Species peculiarities

Strain-related considerations

Typical study protocols

Carcinogenicity toxicity testing

Inhalation and intratracheal studies

Toxicology studies

Chinese hamster ovary (CHO) cell chromosome aberrations assay

Syrian hamster embryo (SHE) cell transformation assay

Models of diseases

Cardiomyopathy

Dental caries

Diabetes mellitus

Leprosy

Muscular dystrophy

Osteoarthritis and degenerative joint disease

Pancreatic cancer

Concluding Remarks and Future Directions

References

3 Minipig models for toxicity testing and biomarkers

Man and his beasts

Use of pigs in biomedical research

Nonrodent species in toxicology

Minipig breeds

Minipigs in Toxicological Testing

Case studies, small molecular drugs

Use of minipigs in biotechnology-derived pharmaceuticals

Summary - minipig in toxicological testing

Biomarker Development and Qualification

Standard Biomarkers used in Minipig Toxicological Studies

Operational standards

Clinical pathology

Coagulation parameters

Urinalysis

Other biomarkers

Normal reference values

Summary - biomarkers

Excipients and Vehicles

Investigation of vehicle and excipients used in minipigs

Other excipients and vehicles.

Histamine release - anaphylactoid reactions

Summary - excipients and vehicles

Future use and Challenges

Toxicological studies

Small molecules - beyond dermal

Large molecules - beyond nonhuman primate

Biomarkers

4 Nonhuman primates in preclinical research

Nonhuman Primates as Animal Models

Clinical Pathology in Nonhuman Primates

Preanalytical variation

Hematology

Coagulation and hemostasis

Clinical biochemistry

Background Lesions in Nonhuman Primates

Mononuclear cell infiltrates

Cardiovascular

Gastrointestinal and hepatic

Renal

Skeletal muscle

5 Biomarkers of toxicity in zebrafish

Zebrafish Background

Ecotoxicological Biomarkers of Toxicity

Examples of Biomarkers of Fish Toxicity

An Example of an Established Biomarker: Vitellogenin

Cautions

Acknowledgments

6 Caenorhabditis elegans as a model for biomarkers of diseases and toxicities

C. Elegans and Biomarkers

Biomarkers for General Organ Damage

Liver

Kidney

Heart

Neurodegenerative Diseases

Alzheimer's disease

Parkinson's disease

Cancers

Breast cancer

Colon cancer

Prostate cancer

Lung cancer

7 Alternative animal toxicity testing and biomarkers

Use of Alternatives to Animal Testing and Biomarkers

Reasons for Developing Alternatives to Animal Tests and the Role of Biomarkers

Examples of Organizations Researching and Funding Alternatives to Animal Testing and Biomarker Development

Achieving 3Rs with Minimal to no Animal Testing by using Biomarkers.

In Silico computer simulation

In Vitro cell culture techniques

Limitations of alternative In Vitro tests

Applications of In Vitro Tests and Biomarkers

Genetic toxicology testing, In Vitro

Bacterial mutation assay (Ames assay)

In Vitro micronucleus and chromosome aberration assays in cultured cells (Cytogenetic assays)

Comet or single cell gel electrophoresis assay

Integrated genotoxicity testing using fewer animals and collecting most information

A unique zebrafish model

In Vitro pharmacologic activity testing

Isolated tissues

Receptor binding studies

In Vitro drug disposition studies

Major challenges of In Vitro ADME

Advances in technologies

Systemic toxicity testing in product development

8 Toxicokinetic-toxicodynamic modeling

Toxicokinetic Models

Toxicant disposition

Classical compartmental toxicokinetic models

Noncompartmental analysis of toxicokinetic data

Physiologically based toxicokinetic models

Toxicodynamic Models

II: Systems Toxicity Biomarkers

9 Central nervous system toxicity biomarkers

Measuring CNS Dysfunctions

Biomarkers in Neurotoxicology

Biomarkers of exposure

Biomarkers of susceptibility

Biomarkers of effects

A Case Study: The Organophosphorus Insecticides

Toxicity and neurotoxicity of OPs

Biomarkers of effect

10 Peripheral nervous system toxicity biomarkers

Organization of the Nervous System

Types of Biomarkers of the PNS

PNS Biomarkers Based on Mechanisms

PNS Biomarker Methodology

Neurological and physical examination.

Sample Requirements for Biomarker Testing.

Notes:

Description based on publisher supplied metadata and other sources.

Other Format:

Print version: Gupta, Ramesh C. Biomarkers in Toxicology

ISBN:

9780124046498

OCLC:

870225412