Conventional Test Method:

Long-Term (2 year) Rodent Carcinogenicity Bioassay (OECD TG 451) AND Chronic Toxicity Studies (OECD TG 452)

Alternative Test Method:

Name & Description:

Cell Transformation Assays

1.Syrian hamster embryo (SHE) assay
2.Balb/c assay
3.C3H/10T1/2 assay

In these assays, carcinogenicity of test substances is determined by measuring phenotypic changes such as cell morphology, colony growth patterns and cell adhesion induced by chemicals in mammalian cell cultures. The most widely used of these assays are the Syrian hamster embryo (SHE) assay, the low-pH SHE assay, the Balb/c 3T3 assay, and the C3H/10T1/2 assay. The SHE assay is believed to detect early steps of carcinogenesis, and the Balb/c and C3H10 assays detect later carcinogenic changes.

Validation Status:

EU: ECVAM is currently conducting validation studies on SHE and Balb/3T3 cell transformation assays in collaboration with US and Japanese labs.

Regulatory Status:

OECD: Draft new test guidelines proposed for SHE assay and Balb/3T3 assay

EU:  Method B.21

Effect or Potential Effect on Animal Use:

Replacement

OR

Reduction
(if part of a tiered testing strategy that results in use of fewer animals)

References:

• Combes R., Balls M., Curren R., Fischbach M., Fusenig N., Kirkland D., Lasne C., Landolph J., LeBoeuf R., Marquardt H., McCormick J., Müller L., Rivedal E., Sabbioni E., Tanaka N., Vasseur P. and Yamasaki H. (1999) Cell transformation assays as predictors of human carcinogenicity – the report of ECVAM workshop 39. ATLA 27(5):745-767.
• European Commission (2012) EURL ECVAM issues recommendation on three alternative-to-animal testing methods for carcinogencity.
• Maurici D., Aardema M., Corvi R., Kleber M., Krul C., Laurent C., Loprieno N., Pasanen M., Pfuhler S., Phillips B., Prentice D., Sabbioni E., Sanner T. and Vanparys P. (2005) Carcinogenicity. ATLA 33(Suppl.1):177-182.
• OECD (2007) Detailed review paper on cell transformation assays for detection of chemical carcinogens, Series on Testing and Assessment No. 31.
• Vanparys P., Corvi R., Aardema M., Gribaldo L., Hayashi M., Hoffmann S. and Schechtman L. (2011) ECVAM prevalidation of three cell transformation assays. ALTEX 28(1):56-59.

Information Last Reviewed:

May 2012