Conventional Test Method:

Mouse LD₅₀ Assay for Botulinum Toxin Potency Testing

Alternative Test Method:

Name & Description:

Non-Lethal Clinical Endpoint in the Mouse LD₅₀ Assay Protocol

This method for the mouse LD50 assay uses Stage Three clinical symptoms (severe indrawn scaphoid abdomen with respiratory distress in the form of hiccough & pupillatory dilation [eyes wide open, bulging]) in place of death as the assay endpoint.

Validation Status:

Canada: Validated by Health Canada

US:  ICCVAM workshop panel recommended that an international validation study using the same non-lethal endpoint be conducted (2008)

Regulatory Status:

Canada: Accepted for use

Effect or Potential Effect on Animal Use:

Refinement
(Does not rely on death as an endpoint)

References:

• Adler S., Bicker G., Bigalke H., Bishop C., Blümel J., Dressler D., Fitzgerald J., Gessler F., Heuschen H., Kegel B., Luch A., Milne C., Pickett A., Ratsch H., Ruhdel I., Sesardic D., Stephens M., Stiens G., Thornton P.D., Thürmer R., Vey M., Spielmann H., Grune B. and Liebsch M. (2010) The current scientific and legal status of alternative methods to the LD50 test for Botulinum neurotoxin potency testing. ATLA 38(4):315-330.
• ICCVAM (2008) Report on the ICCVAM-NICEATM/ECVAM Scientific Workshop on Alternative Methods to Refine, Reduce or Replace the Mouse LD₅₀ Assay for Botulinum Toxin Testing. Bethesda MD: National Institutes of Health (NIH).

Information Last Reviewed:

May 2012