aUse of the crude and adjusted human models produces very similar results (difference of less than 1).
bThe lower value uses the adjusted human model (male, 70 years residency); the higher value uses the crude human model.
mg/kg/day for the four experimental groups (divide fluoride intake, µg/day, by body weight for each water concentration and each time interval: 3, 6, 12, and 18 months). At each water concentration, the doses decrease over time. Compute the time-weighted average dose. That does not account for absorption, but feed intake is a small fraction of the total, especially for higher doses. Figure D-2 plots the average doses versus bone fluoride for both studies. Use of average dose reduces the difference in slopes between the Dunipace and NTP studies but not very much. Dunipace et al. found that bone fluoride concentrations increased very rapidly in the first 3 months, followed by a slow increase. As a result, average dose might not be the best metric. On the basis of water consumption rates, exposures appear similar at 3 months (C. Turner, Indiana University, personal communication). Calcium concentrations in feed were higher in the NTP study (0.6 ppm) than in the Dunipace study (0.5 ppm), reducing fluoride absorption (C. Turner, Indiana University, personal communication). The slope estimated for the Maurer data lies between the other two, but the results of this experiment appear to be nonlinear.
To estimate dose for the Zipkin data, the committee assumed the same water consumption (2 L/day) and body weight (70 kg) for every subject, based on standard the U.S. Environmental Protection Agency figures. This assumption multiplies the slope calculated earlier by a constant, 70/2.
The right-hand column of Table D-2 compares human and rat fluoride uptake on an average dose basis. The ratio of the slopes has increased to 20 to 40. The ratios would be higher if a smaller water consumption rate for humans had been assumed. The very high bone concentration predicted by Rao et al. (1995) for women exposed to fluoride in drinking water at 4 mg/L for 70 years suggests an even higher ratio.
Because many assumptions were involved in estimating the values presented in Table D-2, they should be used with caution. But values support a rat-to-human conversion factor for bone fluoride uptake of at least an order of magnitude.