Reply to Comment on “Effects of Triclocarban, Triclosan, And Methyl Triclosan on Thyroid Hormone Action and Stress in Frog and Mammalian Culture Systems”

Abstract

Reply to Comment on "Effects of Triclocarban, Triclosan, And Methyl Triclosan on Thyroid Hormone Action and Stress in Frog and Mammalian Culture Systems" I n the comment by Fort et al regarding our recent publication by Hinther et al., 1 the authors expressed concern that our synopsis of their previous work 2 was misrepresenting the results described therein and that acknowledgment or discussion of the supplemental data provided in their response to our letter to the editor regarding that work was lacking. 3,4 We maintain that our synopsis of their manuscript was accurate. In this manuscript, 2 tadpole developmental stage was reported as not significantly different compared to controls at day 21 of triclosan exposure. However, the data presented in the manuscript, when reanalyzed by us 3 and subsequently again by the authors 4 demonstrate that there indeed was a significant acceleration of Xenopus laevis tadpole development due to triclosan exposure. Our Chi square analysis of the frequency data presented in the Fort et al. paper 2 showed clear significance in the three lower of the four concentrations tested (0.6, 1.5, 7.2, and 32.3 μg/L triclosan) compared to control animals (for a detailed rationale and analysis refer to ref 3). Using MannÀWhitney U tests, 4 Fort et al. showed a significant acceleration in development at 0.6 and 7.2 μg/L triclosan. We therefore agree with Fort et al that a statistical acceleration of Xenopus laevis tadpole development occurred.A significant increase in TRβ mRNA transcript levels were observed at 1.5 and 7.2 μg/L triclosan which were observed in stage-matched metamorphic climax animals. 2 This observation was regarded as not biologically significant by the authors. 2 Dismissing this observation as not biologically relevant due to the absence of a linear concentrationÀresponse relationship disregards well-precedented hormone response phenomena: 3 TRβ mRNA perturbation can be transitory (but biologically important) and present itself as an apparent "inverted U" rather than a linear response at a given time point. 5,6 Therefore, the observation of a perturbation in Fort et al. 2 is consistent with the observed developmental acceleration.The supplemental data 4 referred to in the comment was not peer reviewed and provided insufficient information in order to properly assess the assertions presented therein. However, the work has now been published in Toxicological Sciences 7 allowing for a more thorough assessment of the data. The original publication stated in the abstract that "End points measured to evaluate effects on thyroid-mediated metamorphosis including developmental stage, thyroid histology, TRβ expression, DI-2 and DI-3 expression, and thyroid gland T 4 (thyroxine) and plasma T 4 and T 3 (triiodothyronine) levels were not affected by TCS exposure." However, it is evident in the manuscript that three of these thyroid end points did show evidence of thyroid axis disruption (thyroid gland hypertrophy, follicle cell height changes, and alterations of plasma T 4 levels). A de...

Reply to 2nd Comment on “Effects of Triclocarban, Triclosan, And Methyl Triclosan on Thyroid Hormone Action and Stress in Frog and Mammalian Culture Systems”

“…This study was followed by a nonstandard modification of this assay that comprised a 32-day exposure beginning with NF stage 47 tadpoles . As indicated in previous correspondences, we disagree with the authors’ data interpretation and conclusions. − The authors dismissed several instances where significant effects on thyroid axis end points were evident. Subsequent mTCS and TCC studies are not yet published in the peer-reviewed literature and, as such, the relevant data needed to evaluate the statements presented in DeLeo et al are currently unavailable.…”