Fig. 3: Establishing correlative human-mouse dosimetry.
From: Immunocompetent cell targeting by food-additive titanium dioxide
a–l Confocal reflectance microscopy showing the range of cellular loading in the subepithelial dome tissue region of (a–f), six randomly-drawn human and (g–l) six randomly-drawn mouse samples. After acquisition, the image-fields per specimen were manually laid out in order of lowest-to-highest fgTiO2 SED accumulation to visually present the wide variation in fgTiO2 cellular loading. Translucent red circle-markers were placed on thresholded reflectant foci to aid visualisation. m–p Quantitative analysis of the image-data shown in (a–l) (n = 6 mice / n = 6 humans). m Thresholded reflectance per unit tissue area (i.e., amount of fgTiO2 per unit tissue area). n Thresholded reflectance per cell (i.e., fgTiO2 dose per cell). o, Number of thresholded reflectant foci per cell (i.e., number of fgTiO2-loaded vesicles (TLV) per cell). p Thresholded reflectance signal per foci (i.e., fgTiO2 dose per TLV). Statistical comparison of the distributions is presented in Supplementary Fig. 6 (two-sided Wilcoxon rank-sum analysis). None of the sets of measured fgTiO2 distributions were found to be entirely unique to either species. m–p By all of the quantitative measures established, feeding a murine diet supplemented with 0.0625% (w/w) fgTiO2 for eighteen weeks provides significant overlap with measured, real-world human exposures. Scale bars: a–l = 50 μm with insets 10 μm; n = 20 μm; p = 5 μm.
