Testing and Three Rs

Toxicity Testing

Regulations and guidelines exist for the safe marketing, labelling, and (in some cases) transportation of chemicals, pesticides, pharmaceuticals, and consumer products. Many of the provisions require manufacturers to conduct testing to identify potential hazards to human and animal health, and to submit the test data to regulatory authorities. Most of the toxicity tests for hazard assessment are animal tests that were developed decades ago. There are many scientific, ethical, and economic advantages to replacing these animal toxicity tests with non-animal (in vitro and in silico) test systems.

(This section has been adapted from AltTox.org)

For more information on toxicity testing the following resources may be useful:

Online resources

• AltTox.org

  - This organization aims to advance non-animal methods of toxicity testing. It is produced through the collaboration of Procter & Gamble Company (P&G) and the Humane Society of the United States (HSUS). The website's informational section, Toxicity Testing Resource Center (TTRC), provides a comprehensive source of information on non-animal methods of toxicity testing.

• CAAT TestSmart

  The Johns Hopkins Center for Alternatives to Animal Testing (CAAT) established a toxicology risk assessment model called TestSmart, and seeks to identify newer, better testing methods than those commonly used or accepted today. TestSmart symposiums have been held on the following topics: High Production Volume (HPV) Chemicals, Pharmaceutical Safety Assessment, Endocrine Disruptors, and Developmental Neurotoxicity. Proceedings and recommendations from these workshops can be accessed online.

• Chapman K. & Robinson S. (2007) Challenging the regulatory requirement for acute toxicity studies in the development of new medicines: A workshop report. The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).
• Committee on Toxicity Testing and Assessment of Environmental Agents, National Research Council (2007) Toxicity Testing in the 21st Century: A Vision and a Strategy, The National Academies Press, Washington (DC, US)
• European Centre for the Validation of Alternative Methods (ECVAM) Workshop Reports.
• Humane Society of the United States (HSUS) (2002) Workshop on Refinements in Toxicology testing.

  A collection of papers was prepared following a workshop hosted by the HSUS in New Orleans on March 14, 1999 on the subject of refinement in toxicological methods:

  • Contag P.R. & Contag C.H. Refinement of animal models by noninvasive monitoring of infection and gene expression.
  • Doerning B. Effects of routine animal husbandry and experimental procedures on physiological parameters of rats.
  • Fentener van Vlissingen J.M., Kuijpers M.H.M., van Oostrum E.C.M., Beems R.B. & van Dijk J.E. Retrospective evaluation of clinical signs, pathology and related discomfort in chronic studies.
  • Levine B. Relationship between dosing vehicles, dose volume, & stress.
  • Richmond J. Dosing limit volumes: the United Kingdom view-past and present
  • Schlede E., Diener W. & Gerner,I. Humane endpoints in toxicity testing.
  • Smith D. Dosing limit volumes: a European view.

• The NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) (2008) NICEATM-ICCVAM 5-Year Plan (2008-2012). Bethesda MD: NIH.
• Smith D. & Trennary P. (2002) Non-rodent selection in pharmaceutical toxicology. 8pp. Association of the British Pharmaceutical Industry (ABPI) & UK Home Office

Other publications

• Phillips B., Smith D., Combes R., Descotes G., Jacobsen S.D., Hack R., Kemkowski J., Krauser K., Pfister R., Rabemampianina Y., Sparrow S., Stephan-Gueldner M. & von Landenberg F. (2004) An approach to minimise dog use in regulatory toxicology: production of a best practice guide to study design. ATLA 32(Suppl. 1):447-451.
  
  
• Robinson S., Delongeas J.- L., Donald E., Dreher D., Festag M., Kervyn S., Lampo A., Nahas K., Nogues V., Ockert D., Quinn K., Old S., Pickersgill N., Somers K., Stark C., Stei P., Waterson L. & Chapman K. (2008) A European pharmaceutical company initiative challenging the regulatory requirement for acute toxicity studies in pharmaceutical drug development. Regulatory Toxicology & Pharmacology. 50:345-352
  
  
• Smith D., Combes R., Depelchin O., Jacobsen S.D., Hack R., Luft J., Lammens L., von Landenberg F., Phillips B., Pfister R., Rabemampianina Y., Sparrow S., Stark C. & Stephen-Gueldner M. (2005) Optimising the design of preliminary toxicity studies for pharmaceutical safety testing in the dog. Regulatory Toxicology & Pharmacology 41:95-101.
  
  
• Whitehead A. & Stallard N. (2004) Opportunities for reduction in acute toxicity testing via improved design. ATLA 32(Suppl. 2):73.

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