Evaluation of FETAX for Developmental Toxicity

In 1998, EPA requested that ICCVAM evaluate the frog embryo teratogenesis assay – Xenopus (FETAX). An ICCVAM-sponsored expert panel concluded that FETAX was not sufficiently validated or optimized for regulatory applications. The panel recommended the following:

• Standardize FETAX to reduce variability.
• Increase the number of endpoints assessed in the assay.

Minutes of the ICCVAM-sponsored Expert Panel Meeting (2000)
Background Review Document: Frog Embryo Teratogenesis Assay – Xenopus (FETAX) (March 2000)

Background

Developmental toxicity testing evaluates the extent to which exposure to a substance can interfere with normal development. Effects of developmental toxicants can be obvious or subtle, and may be apparent at birth or emerge later in the offspring's life. Current U.S. federal regulations require testing of many substances and products, such as pesticides, food additives, industrial chemicals, and pharmaceuticals, for their potential to cause developmental toxicity.

Most developmental toxicity tests use rabbits or rats, but other mammalian species may be used. FETAX is a 96-hour test that uses early-stage whole embryos of the South African clawed frog (Xenopus laevis) to measure the potential of substances to cause mortality, malformation, and growth inhibition in developing embryos.

FETAX was nominated by EPA as a screening assay to identify potential human developmental toxicants. In response to the nomination, ICCVAM agreed to consider the potential regulatory applications of FETAX. NICEATM prepared a background review document summarizing available data on FETAX and the extent to which the assay met ICCVAM validation and acceptance criteria for potential regulatory applications. The NICEATM background review document was considered in 2000 by an ICCVAM-sponsored expert panel charged to review the current status and future directions for FETAX method development.

Related Reference

A subsequent review (Hoke and Ankley, 2005) provides an evaluation and critique of the current FETAX protocol from two perspectives:

• Practical considerations relative to conducting the test.
• Sensitivity of the assay (and associated endpoints) compared to tests with other species.