Mutagenesis, Volume 31, Issue 3, 1 May 2016, Pages 309–321, https://doi.org/10.1093/mutage/gev070
The author would like to inform readers that the Figures 2, 3 and 4 in this manuscript were incorrectly numbered and had incorrect legends. The figures appear below correctly.
Figure 2.
BMD10 analysis of in vitro MN dose responses in Chinese hamster ovary (CHO-K1) cells following exposure to the benzimidazoles, oxibendazole (grey), flubendazole (light blue), mebendazole (pink), albendazole (black), carbendazim (dark blue), benomyl (green) and albendazole oxide (red) (19). The figure was modified from the article (37). The top figure shows that the four parameter (m5-bv) exponential model provided a suitable fit to each dose response using the compound as covariate for BMD analysis. The dotted lines show the BMD10 derivations for each dose response, and these correspond to the mid-point for each line plotted in the bottom figure. These lines in the bottom graph span the BMDL10 to the BMDU10 derived from the top figure using PROAST v50.8. Flubendazole, oxibendazole and mebendazole grouped together along with albendazole. Benomyl and carbendazim also grouped together with albendazole oxide being a lot less potent and forming no groupings. The individual plots are located in Supplementary Figure 2.
Figure 3.
BMD10 analysis of in vitro MN dose responses in human lymphocytes albendazole (green) flubendazole (black), R-reduced flubendazole (dark blue), S-reduced flubendazole (light blue) and albendazole sulfoxide (red), in human lymphocytes. The top figure shows that the four parameter (m5-bv) exponential model provided a suitable fit to each dose response using the compound as covariate for BMD analysis. The dotted lines show the BMD10 derivations for each dose response, and these correspond to the mid-point for each line plotted in the bottom figure. These lines in the bottom graph span the BMDL10 to the BMDU10 derived from the top figure using PROAST v50.8. Albendazole and flubendazole were equipotent, and the R- and S-metabolites of flubendazole were less potent and of similar potency to albendazole sulfoxide. Hydrolysed flubendazole showed no dose response using BMD analysis and was omitted from this covariate analysis.
Figure 4.
In vivo MN dose responses from the rat study outlined in Table 4. BMDS was used to defined BMD1SD metrics, and log transformed response data provided a normal distribution and homogeneous variance as measured through the Shapiro–Wilks and Bartlett’s test, respectively, so were used for the analysis (35). The polynomial model was the most suitable for these data. A BMD1SD, 18.9699 and BMDL1SD, 14.6483 were derived from this model. A reference dose (RfD) calculated using this value would be calculated a scaling factor of 0.16 for rat to human, 60 kg person, and an uncertainty factor of 10 for unknown differences; [(14.6483 × 0.16 × 60)/10] × 1000 = 14.06 mg/person/day. Note that if the uncertainty is taken into account by use of the lower bound of the BMD1SD (BMDL1SD) compared with the BMD1SD or the NOGEL, then this factor of 10 is removed and you obtain a reference dose = 140.62 mg/person/day.
The manuscript has been corrected online.