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Basic Elements of Toxicology

Basic Science

  1. Bryan Ballantyne MD, DSc, PhD, FRCPath, FFOM, FACOEM, FAACT, FATS, FIBiol, CBiol1,
  2. Timothy C. Marrs OBE, MD, DSc, FRCP, FRCPath, FBTS, FATS2,3,4,
  3. Tore Syversen MSc, Dr Philos5

Published Online: 15 DEC 2009

DOI: 10.1002/9780470744307.gat001

General, Applied and Systems Toxicology

General, Applied and Systems Toxicology

How to Cite

Ballantyne, B., Marrs, T. C. and Syversen, T. 2009. Basic Elements of Toxicology. General, Applied and Systems Toxicology. .

Author Information

  1. 1

    Independent Consultant in Occupational and Clinical Toxicology, Charleston, West Virginia, USA

  2. 2

    Edentox Associates, Pinehurst, Edenbridge, Kent, UK

  3. 3

    National Poisons Information Service (Birmingham Centre) and West Midlands Poisons Unit, Birmingham, UK

  4. 4

    University of Central Lancashire, Lancashire School of Health and Postgraduate Medicine, Preston, UK

  5. 5

    Norwegian University of Science and Technology, Department of Neuromedicine, Faculty of Medicine, Trondheim, Norway

Publication History

  1. Published Online: 15 DEC 2009
Table 1. Major Driving Forces for the Development and Increasing Specialization of the Scientific Basis and Applications of Toxicology
  • Exponential increase in the number of synthetically produced industrial and domestic chemicals

  • Major increase in the numbers and nature of new drugs, pharmaceutical preparations, tissue-implantable materials and medical devices

  • Increase in the number and nature of pesticides and related products

  • Growing concern about the number of food-additive materials

  • Increasing concern that environmental agents, including pesticides, chemical pollutants and naturally occurring toxins, are contributing to the causation and pathogenesis of diseases, in particular cardiovascular, neurological, pulmonary and neoplastic.

  • Mandatory testing and regulation of chemicals and drugs used commercially, domestically and medicinally

  • Enhanced public awareness of the potential for adverse effects from xenobiotics and naturally occurring chemicals to man, animals and the general environment

  • The potential for interactions between occupational, domestic and environmental exposures and its influence on adverse effects

  • Litigation, principally as a consequence of occupationally related illness, unrecognized or poorly documented product safety concerns and environmental harm. Recently, certain lawyers (of the ambulance-chasing type) are inserting advertisements on television to draw attention of the general public to adverse drug effects and offering their services for litigation against companies and prescribers (a practice that will have detrimental implications for future drug development)

  • Activities of public awareness and ‘watchdog’ groups

Table 2. Major Subspecialties of Toxicology
SpecialtyMajor functional components
LaboratoryDesign and conduct of in vivo and in vitro toxicology testing programmes
RegulatoryAdministrative function concerned with the development and interpretation of mandatory toxicology testing programmes, and with particular reference to ensuring the safe use, handling and transportation of substances used commercially, domestically and therapeutically, and with the development of product-safety literature and labels
ClinicalThe causation, diagnosis and management of poisoning in humans
VeterinaryThe causation, diagnosis and management of poisoning in domestic and wild animals
ForensicEstablishing the cause for death or intoxication in humans, by analytical procedures, and with particular reference to legal processes
OccupationalDetermining the potential for adverse effects from chemicals and other agents in the occupational environment and the development of appropriate screening procedures and precautionary and protective measures
ProductAssessing the potential for adverse effects from commercially produced chemicals and formulations, and development of recommendations on safe patterns, protective and precautionary measures, and development of relevant literature for users
PharmacologicalAssessing the toxicity of therapeutic agents
AquaticAssessing the toxicity to aquatic organisms of chemicals discharged into marine and fresh waters
EnvironmentalDetermining the adverse effects of toxic pollutants, usually at low concentrations, released from commercial, industrial, domestic and natural sources into the immediate environment and subsequently widely distributed by air and water current and by diffusion through soil. It differs from ecotoxicology (see below) in focussing on the effects on individuals
EcotoxicologyDetermining adverse effects and impact from synthetic or natural pollutants on populations, communities, and terrestrial, freshwater and marine animal, vegetable and microbial ecosystems. If differs from environmental toxicology (see above) in that the aim is to integrate the effects at all levels of biological organization from molecular to whole communities, and therefore is a broader discipline.
ToxicologyDetermining the toxicity of substances of biological origin, including plants, animals and pathogenic microorganisms
Table 3. Examples of Toxic Effects Classified According to Timescale and Location
Exposure timeLocationEffectSubstance
AcuteLocalSkin corrosionMethylamine
  Lung injuryHydrogen chloride
 SystemicKidney injuryPhenacetin
  HaemolysisArsine
 MixedLung injury and methaemoglobinaemiaOxides of nitrogen
Short-termLocalSkin sensitizationEthylenediamine
RepeatedLocalLung sensitizationToluene di-isocyanate
  Nasal septum ulcerationChromates
 SystemicNeurotoxicityAcrylamide
  Liver injuryArsenic
 MixedRespiratory irritation and neurobehaviouralPyridine
ChronicLocalBronchitisSulphur dioxide
  Laryngeal carcinomaNitrogen mustard
 SystemicLeukaemiaBenzene
  Angiosarcoma (liver)Vinyl chloride
 MixedEmphysema and kidney injuryCadmium
  Pneumonitis and neurotoxicityManganese
Table 4. Examples of Toxic Effects Classified According to the Time for Development or Duration of the Lesion
TimescaleEffectSubstance
PersistentTesticular injuryDibromochloropropane
 Scarring (skin/eye)Corrosives
 Pleural mesotheliomaAsbestos
TransientNarcosisOrganic solvents
 Sensory irritationAcetaldehyde
CumulativeSquamous metaplasiaFormaldehyde
 Liver fibrosisEthanol
LatentPulmonary oedemaPhosgene
 Peripheral neuropathyAnticholinesterase organophosphates
 Pulmonary fibrosisParaquat
Table 5. Examples of the Metabolic Transformation of Chemicals
BiotransformationChemicalConversion
DetoxificationCyanideEnzymatic conversion to less toxic thiocyanate
 Benzoic acidConjugation with glycine to produce hippuric acid
 Bromobenzene3,4-Epoxide reactive metabolite is enzymatically hydrated to the 3,4-dihydrodiol or conjugated with glutathione
ActivationCarbon tetrachlorideMicrosomal enzyme metabolic activation to hepatotoxic trichloromethylperoxy radicals
 2-AcetylaminofluoreneN-Hydroxylation to more potent carcinogen
  N-Hydroxyacetylaminofluorene
 ParathionOxidative desulfuration to the potent cholinesterase inhibitor paraoxon