Statistical Methods for Estimating LTD10 from TD50 and Its Lower Confidence Limit

LTD10 is the lower 95% confidence limit on the dose to induce tumors in 10% of animals. LTD10 values are estimated from the CPDB using the TD50 and 99% lower confidence limit as follows:

Both the TD50 and the two-sided 99% confidence limits (LoConf, UpConf) are reported in the CPDB from fitting the one-hit model to experimental dose-response data using maximum likelihood methods. The one-hit model was selected because it is the most conservative of the multistage models. When both the TD50 and the two-sided 99% confidence limits are available, it is shown in Gold et al. (2003) for the one-hit model that the lower 95% confidence limit for the TD10, i.e., LTD10 is:

LTD10 = [(TD50)0.36 × (LoConf)0.64] / 6.6

Since the one-hit model is the most conservative form of the family of multistage models of carcinogenesis, the above estimate of the LTD10 provides at least 95% confidence that the true value of the TD10 is above this lower confidence limit for this family of models.

This method gave similar estimates to the LTD10 obtained by fitting the multistage model to the tumor incidence data for both linear and curved dose responses with high or low tumor rates in the controls and tight or wide confidence limits for the TD50 (Gold et al., 2003). Thus, relatively precise estimates of the LTD10 can be readily calculated from the TD50 and LoConf from the CPDB.

LTD10 values are reported in an Excel spreadsheet in each species for all chemicals in the CPDB with a positive evaluation of carcinogenicity by the author of at least one experiment.

See also Statistical Methods for Estimating TD50.


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Last updated: August 6, 2007

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