# Science Advances

## Supplementary Materials

**This PDF file includes:**

- S1. Description of data sets and guide for data analysis
- S2. Supplementary methods
- S3. Table summary of pharmaceutically active pollutants
- table S1.1. Summary of observations by Case and Exp. Group for the GSA.csv data set.
- table S1.2. Summary of the variables included in the GSA.csv data set.
- table S1.3. Summary of observations by Case and Exp. Group for GSA_MIX_MEDIAN data set.
- table S1.4. Summary of the variables included in the GSA_MIX_MEDIAN.csv data set.
- table S1.5. Summary of observations by Exp. Group for ANTIBIOTIC_EC50.csv data set.
- table S1.6. ANTIBIOTIC_EC50.csv data set.
- table S1.7. Summary of observations by Exp. Group for biofilm.csv data set.
- table S1.8. biofilm.csv data set.
- table S1.9.
*P*values of Wald test for significance of time variable of the ANODEV test for each univariate GLMs fitted to each end point (Phos, Gluc,*F*_{0},*Y*_{max},*F*,*Y*_{eff}) for each treatment with time as explanatory variable. - table S2.1. Number of observations for calculating each occurrence of statistical descriptors.
- table S2.2. Stability of PPCPs under experimental conditions.
- fig. S1.1.
*Q*-*Q*plot for normal distribution for control observations (*n*= 880). - fig. S1.2. Notched box plot for Lum of control observations by Experiment.
- fig. S1.3. hovPlots for bioluminescence as a function of the Experiment for Control observations.
- fig. S1.4. hovPlots for bioluminescence as a function of the Experiment for Treatment observations.
- fig. S1.5. Notched box plot for Lum of controls (
*n*= 880), individual exposure to PPCPs (*n*= 768), and exposure to mixtures of PPCPs (*n*= 1080). - fig. S1.6. 95% family-wise confidence level for the difference of means according to anova.2_glht model.
- fig. S1.7. Notched box plot for Lum of control observations (
*n*= 880), divided into two aleatory groups C1 (*n*= 440) and C2 (*n*= 1080). - fig. S1.8. Notched box plot for Lum for treatment observations shorted by L level (1, 2).
- fig. S1.9. Boxplots of Lum as a function of PPCPs (C1 to C16).
- fig. S1.10. Histogram (left panel), normal Q-Q plot (central panel) and jack after
jackknife plot (right panel) for bootstrapped medians of Lum values (
*R*= 999) for “treatment” = 1. - fig. S1.11. Bootstrapped (
*R*= 999) medians and 95% CIs for the 180 treatments. - fig. S1.12. Tolerance level in the estimation of median values for lum for the 180 mixture effects.
- fig. S1.13. EE μ*-σ plot for the 17 studied input factors (16 PPCPs and light intensity).
- fig. S1.14. Ranked input factors by importance (μ*).
- fig. S1.15. EE μ*-σ plot for the 17 studied input factors (16 PPCPs and light intensity).
- fig. S1.16. Diagnostic plots of Anov.1 model.
- fig. S1.17. Diagnostic plots of Anov.4 model.
- fig. S1.18. Dose ranges of PPCPs (in nanograms per liter).
- fig. S1.19. Histogram of the frequency distribution of the total sum of the 16 PPCPs in the 180 mixtures.
- fig. S1.20. Rose plot presenting the relative abundance (counts) of each PPCP (variable) and level (value) of each PPCP in the 180 mixtures.
- fig. S1.21. Rose plot presenting the mean concentration (value) of each PPCP (variable) in the 180 mixtures.
- fig. S1.22. Dose-response data and fitted LL5 drm models (chem.1) to the experimental data according to CA model.
- fig. S1.23. Schematic representation of the calculation sequence required to predict chemical mixture effects.
- fig. S1.24. The 21 dose-response models (LL.5 models) fitted to the in silico–predicted dose-response patterns of the 21 unique combinations of C10, C11, and C14.
- fig. S1.25. Observed versus predicted bioluminescence values of A. CPB4337 to the 180 low-dose mixtures of PPCPs.
- fig. S1.26. FITEVAL report for the predicted versus experimental low-dose mixture effects of PPCPs.
- fig. S1.27. Response of six community-level end points measured along time as a function of treatment on model freshwater benthic microbial communities.
- fig. S1.28. Residual versus fits plot to check the quadratic mean-variance assumption of negative binomial regression (with different metabolic end points coded in different colors).
- References (
*73*–*109*)

**Other Supplementary Material for this manuscript includes the following:**

- S4 (Microsoft Excel format). Composition of the 180 mixtures

**Files in this Data Supplement:**