Alternative testing methods

Nicklasson M, Langenbucher F. Description and evaluation of the flow cell dissolution apparatus as an alternative test method for drug release. Pharm Forum 1990 16(3) 532-537. 

ICCVAM has evaluated alternative test methods for acute oral toxicity, genetic toxicity, biologies, immunotoxicity, dermal corrosion and irritation, ocular toxicity, developmental toxicity, pyrogeni-city, and endocrine disrupter effects (ICCVAM 2007). As examples, alternative test systems for dermal corrosion and irritation are described in the following text. 

The duties of ECVAM are to coordinate the validation of alternative test methods at the EU level, to act as a focal point for the exchange of information on the development of alternative test methods, to set up, maintain, and manage a database on alternative procedures, and to promote dialogue between legislators, industries, biomedical scientists, consumer organizations, and animal welfare groups, with a view to the development, validation, and international recognition of alternative test methods. 

ECVAM has validated alternative test methods for acute oral toxicity, biologies, immunotoxicity, dermal corrosion and irritation, developmental toxicity, and pyrogenicity (ECVAM 2007). 

The embryonic stem cell test is an animal-free alternative test method for developmental toxicity. Mouse embryonic stem cells are cultured in a hanging drop method to form embryoid bodies. These embryoid bodies, when plated on tissue culture dishes, differentiate to form contracting myocardial cell foci within 10 days. Inhibition of cardiomyocyte differentiation by test compounds serves as the end point of the assay, as monitored by cormting contracting muscle foci under the microscope. 

Key words Embryonic stem cell test. Embryonic stem cells. Alternative test method, Cardiomyocyte differentiation. Developmental toxicity... 

ECVAM is the leading international center for alternative test method validation. Hartung et al. (29) summarized the modular steps necessary to accomplish stage 3 (test validation). The seven modular steps are (I) test definition, (2) within-laboratory variability, (3) transferability, (4) between-laboratory variability, (5) predictive capacity, (6) applicability domain, and (7) performance standards (29). Steps 2-4 evaluate the test s reliability steps 5 and 6 evaluate the relevance of the test. Successful completion of all seven steps is necessary to proceed to stage 4 (independent assessment or peer review). This modular approach allows flexibility for the validation process where information on the test method can be gathered either prospectively or retrospectively. The approach is applicable not only to in vitro test methods but also to in silico approaches (e.g., computer-based approaches such as quantitative structure-activity relationships or QSAR) and pattern-based systems (e.g., genomics and proteomics). 

KoCVAM was announced in 2009 and established in 2010. In March 2011, KoCVAM joined the 2009 agreement known as the International Cooperation on Alternative Test Methods (ICATM) that had previously been formed with Europe, Canada, the USA, and Japan (33). This agreement will promote international cooperation on the validation of new test methods. It is envisioned that this cooperative effort will result in the most vigorous and robust science, thereby promoting regulatory acceptance. 

ICCVAM (2003) ICCVAM guidelines for the nomination and submission of new, revised, and alternative test methods. http //iccvam. niehs.nih.gov/SuppDocs/SubGuidelines/ SD subg034508.pdf. Accessed 28 Sept 2011... 

It is worth remembering, and this is applicable also to adhesion to fabrics or any other substrate, that adhesion is only a tiny part of testing rubbers whereas it is the prime consideration for adhesives. Hence, for a fuller understanding of the relevance and limitations of adhesion tests as well as for alternative test methods it is suggested that reference should be made to the great volume of literature from that industry. 

It is important that the protocol has provisions for deviations and corrections, as well as cases in which an alternative test method would have to be used because of test equipment problems. This could prevent having to repeat the entire validation. 

Sailstad, D. M. Murine local lymph node assay An alternative test method for skin hypersensitivity testing. Lab. Animal 31 36-41, 2002. 

Therefore, an alternative test method, such as heating at 80 °C for 2 h, an alkali modified Coomassie-dye assay (e.g. Boyes et al. 1997), or the more recently available reagent based test kits such as Proteotest or Prostab, could present an opportunity to decrease bentonite dose and reduce volume of wine occluded in bentonite lees if confirmed to predict more accurately haze formation in wine. If these alternative test methods could replace the current heat test method of 80 °C for 6 h, this would also reduce the amount of time and/or effort presently required by a winery s laboratory to conduct heat stability testing. 

Materials and articles in contact with foodstuffs - Plastics - Part 15 Alternative test methods to migration into fatty food simulants by rapid extraction into iso-octane and/or 95% ethanol... 

During the early validation studies, the evaluated alternative test methods showed good reproducibility, but no single method was found able to replace the animal test. The main reasons for such an outcome were as follows (a) the variability of the in vivo eye irritation responses, which are linked to the subjectivity of scoring and variability of animal responses (b) the in vitro tests, which... 

It is generally accepted that, in the foreseeable future, no single in vitro eye irritation test will be able to replace the in vivo Draize eye test to predict across the full range of irritation for different chemical classes. However, strategic combinations of several alternative test methods within (tiered) testing strategies may be able to replace the Draize eye test. 

The acid number—the quantity of base, expressed in milligrams of potassium hydroxide per gram of sample, that is required to titrate a sample in this solvent to a green/green-brown end point with p-naphtholbenzein indicator solution (ASTM D-974, IP 139). However, many higher-molecular-weight oil products (dark-colored oils), which cannot be analyzed for acidity because of obscurity of the color-indicator end point, can be analyzed by an alternate test method (ASTM D-664). The quality of the mineral oil products renders them suitable for determination of the acid number. 

One test method (ASTM D-566, IP 132) is not recommended for temperatures above 288°C. In those cases, the alternate test method (ASTM D-2265) should be used. 

It is important to note that some diesel and jet fuels have been formulated with little or no aromatic content. These fuels lack the 810 cm marker band discussed above and alternate IR regions or alternate test methods must be used for fuel measurement. 

ASTM D 7031-04 says (5.21.1) Resistance to fungal decay shall be determined in accordance with accepted methods. Test Method D 2017 (or its alternate Test Method D 1413) is commonly used for this purpose. It also says (Note 11) This is an accelerated laboratory decay test. Results are subjective and comparisons between tests and materials should be used with caution. However, mean specimen weight losses greater than 5% or significantly greater than controls should be cause for concern. ... 

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