ID#

1299

Location:

Exhibit Hall

Time of Presentation:

March 24, 9:30 AM

Category (Subcategory):

In Vitro/Alternative Animal Models, (Skin), (Regulatory/Policy)

Estimate of False Negative Rates for the In Vivo Rabbit Dermal Corrosion Assay
R.R. Tice^1,2, N.Y. Choksi^1,2, J. Haseman³, R. Hill⁴, M. Lewis⁴, D. Lowther⁴, W.S Stokes²
1. ILS, Inc., RTP, NC, USA.
2. NICEATM, NIEHS, Research Triangle Park, NC, USA.
3. NIEHS, RTP, NC, USA.
4. EPA, Washington, DC, USA.
5. FDA, College Park, MD, USA.

Alternative in vitro test methods proposed to substitute or replace an in vivo assay should provide equivalent or improved protection of human or animal health to gain regulatory and general acceptance. ICCVAM evaluated four in vitro dermal corrosivity assays as potential replacements for the in vivo dermal corrosivity assay. ICCVAM recommended that these assays be used in accordance with the globally harmonized tiered testing scheme in a weight-of-evidence approach. In this approach positive substances could be classified and labeled as corrosives and negative substances are further evaluated in accordance with an internationally accepted testing scheme. This recommendation was based largely on the 12-17 percent false negative rates of the in vitro assays in identifying corrosive substances. ICCVAM concluded that these false negative rates likely exceeded that of the currently used in vivo assay and would not provide adequate public health protection. To estimate the likelihood of a false negative result in the in vivo assay, the available data was reviewed. Relevant in vivo dermal corrosivity data were obtained from federal agencies and the published literature. The database consisted of 50 corrosive substances. Since the true likelihood of a corrosive response for each of the substances in the database was unknown, the sample rate was considered the best estimate of the true positive response rate. Initial analysis of the database indicated that the current in vivo dermal corrosivity test has an estimated false negative rate of 5.5 percent. The analysis also suggests that under-classification of a substance would most likely occur only for weak corrosives. NICEATM continues to seek additional high-quality in vivo corrosivity data to refine the estimated in vivo assay false negative rate. This evaluation emphasizes the need for high quality in vivo dermal corrosivity data that can be used to evaluate the performance of proposed alternative assays. ILS staff supported by NIEHS contract N01-ES-35504.