Toxicity testing, methodology

One major deviation from the typical toxicity test methodologies was that field replicates were used for toxicity testing in lieu of the standard laboratory replication (z. e., one replicate per station rather than 5). This modification was made a priori in order to maximize the number of stations at the expense of statistical power within the available project resources. 

Tyl RW and Mart MC (2005) Chapter 7, Developmental toxicity testing - methodology. In Hood RD (ed.) Handbook of Developmental Toxicology. Boca Raton, FL CRC Press. 

Fowler, J. and Rutty, D. (1983). Methodological aspects of acute toxicity testing particularly LD50 determinations Present use in development of new drugs. Acta Pharmacol. Toxicol. 52 (Suppl. 2) 20-30. 

The reader is also referred to the OECD Guidance Document No. 43 on Reproductive Toxicity Testing and Assessment (13), which will form the basis for the methodological points discussed below. More information can also be found in the IPGS paper on principles for evaluating health risks to reproduction associated with exposure to chemicals (14) as well as in an overview paper by Buschmann (15). 

Chial, B.Z. and Persoone, G. (2002) Cyst-based toxicity tests XIII - Development of a short chronic sediment toxicity test with the ostracod crustacean Heterocypris incongruens Methodology and precision, Environmental Toxicology 17 (6), 528-532. 

Designing an appropriate sampling methodology and toxicity test... 

A detailed discussion of experimental in vitro and in vivo testing methodologies and results is not the purpose of this chapter. There are some comprehensive reviews covering this topic. For instance, the contribution by Oberdorster et al. [45] who have summarized recent data and highlighted gaps in this field two works [60, 61] review data on environmental and human effects of carbon nanotubes in relation to their properties a paper [62] that discusses toxicological endpoints of combustion-derived nanoparticles a review [63] of quantum dots toxicity an excellent review devoted to toxicity of particular nanomaterials classes by Borm et al. [26] and many others. 

In the case of noncompendial materials, specifications and complete descriptions of the test methodologies to be used for quality control release purposes by the sponsor should be included. In addition, it may be necessary for the sponsor to obtain a letter authorizing reference to a DMF from the supplier concerning the manufacturing and controls procedures used to make these materials, such as mixtures of colorants or flavors. It may be necessary to obtain toxicity data if the mixture or component has little or no history of human use (e.g., new polymers). If it is anticipated that an untried component will be used, it is recommended that discussions be initiated with the FDA s reviewing chemist and pharmacologist. These sessions should be scheduled as soon as possible to minimize the possibility of delays in NDA approval caused by inadequate information to support use of the material. 

The scientific credibility of the AEGL values is based on adherence to the NRC guidelines (NRC 1993a) for the development of short-term exposure limits, the comprehensive nature of data collection and evaluation, the consistency of the methodologies and procedures used to develop the values, the potential of acute toxicity testing in cases of inadequate data, and the adoption of the most comprehensive peer-review process ever used to establish short-term exposure limits for acutely toxic chemicals. 

Williams, G.M. latropoulos, M.J. Weisburger, J.H. Chemical carcinogen mechanisms of action and implications for testing methodology. Exp. Toxic. Pathol. 1996, 48, 101-111. 

Knight A. Non-animal methodologies within biomedical research and toxicity testing. ALTEX Alternat Tierexp. 2008 25(3) 213-231. 

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