Fig. 1

TCDD-elicited changes in urinary metabolites. Urine was collected from individual mice (n = 5) one day before euthanasia on PND 57 between ZT0-3. Metabolites were normalized by creatinine levels followed by probabilistic quotient normalization. (A) Heatmap of dose-dependent changes in metabolite levels. The black triangle (upper right hand corner) indicates a significant (p ≤ 0.05) change from controls following Benjamini-Hochberg (BH) and post hoc Dunnett’s tests relative to urine from sesame oil gavaged mice. Maximum concentrations are colored according to low (0.25 μM/μM creatinine) and high concentrations (2 μM/μM creatinine). (B) Benchmark dose–response values for metabolites in (A) calculated using BMDExpress2 (v2.3). The 10% benchmark dose (BMD10%) was estimated with a 95% confidence interval to calculate a lower (BMDL10%) and an upper (BMDU10%) bound. The median BMDL10%, BMD10%, and BMDU10% of all significant metabolites (p value ≤ 0.05).