Additional file 1 of Environmental fate and effects assessment of human pharmaceuticals: lessons learnt from regulatory data
Creators: name: Schwarz, Simon
name: Gildemeister, Daniela
name: Hein, Arne
name: Schröder, Patrick
name: Bachmann, Jean
Publisher: name: figshare
Year: 2021
Subjects: subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Biotechnology
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Cancer
subject: Science Policy

description: Additional file 1: Figure S1. Correlation of lipophilicity (highest logDow in environmentally relevant pH-range) and toxicity (lowest NOEC or EC10) in human APIs (n=172). Substances with high logDow tend to have lower effect concentrations. However, there are still several APIs with logDow &lt; 3 and NOEC &lt; 1 μg/L. Figure S2. Depiction of the lowest available NOEC or EC10 available per API, arranged in ascending order. The plot is based on the full dataset (309 APIs). APIs with logDow larger than 3 are coloured orange, APIs with logDow lower than 3 are coloured black. If no reliable data on the logDow is available, the API is coloured grey. Two theoretical distributions are fit (normal distribution based on either log10 or on Box–Cox-transformed dataset). The fitted distribution and calculated 5 % and 1 % NOECs are marked in blue (log10) and red (Box–Cox). The 95 % confidence interval (CI) for the “Box–Cox” model is shown as dashed black line. The 1 %, 5 % and 50 % level are depicted as dashed grey lines. Figure S3. Information on the fitted distribution and goodness-of-fit, based on the Box–Cox-transformed (λ = 0.0202) adjusted dataset (excluding endocrine-active substances and antiparasitics). Figure S4. Information on the fitted distribution and goodness-of-fit, based on the log10-transformed adjusted dataset (excluding endocrine-active substances and antiparasitics). Figure S5. Information on the fitted distribution and goodness-of-fit, based on the Box–Cox-transformed (λ = 0.0606) full dataset (including all API groups). Figure S6. Information on the fitted distribution and goodness-of-fit, based on the log10-transformed full dataset (including all API groups). Figure S7. Overview of the lowest NOECs/EC10s, sorted by pharmaceutical group. Bold lines depict the median, boxes the 25 % and 75 % percentiles, whiskers the 1.5 interquantile ranges. Each black dot represents a single API. A detailed description of the pharmaceutical groups is given in Table S1. Figure S8. Overview of the sensitivity difference between most and least sensitive taxon for 182 APIs, displayed as the quotient of the highest NOEC divided by the lowest NOEC per API. Bold lines depict the median, boxes the 25 % and 75 % percentiles, whiskers the 1.5 interquantile ranges. Each black dot represents a single API. A detailed description of the pharmaceutical groups is given in Table S1. Contrast agents and antiparasitics are excluded because there was data on no, or only one API per group, respectively. Figure S9. Overview of terrestrial effect concentrations, sorted by pharmaceutical group. Bold lines depict the median of the lowest overall effect concentrations, boxes the 25 % and 75 % percentiles, whiskers the 1.5 interquantile ranges. Endpoints for each organism group are illustrated by coloured dots (uncensored values) or crosses (censored values). Green represents plant NOECs/EC10s, orange collembolan NOECs/EC10s and blue annelid LC50s. A detailed description of the pharmaceutical groups is given in Table S1. Figure S10. Depiction of the lowest available NOEC or EC10 available per API, arranged in ascending order. The plot is based on an adjusted dataset only including API with data on all three aquatic taxa; excluding antibiotics, antivirals, antimycotics, antiparasitics and endocrine-active substances (147 APIs). APIs with logDow larger than 3 are coloured orange, APIs with logDow lower than 3 are coloured black. If no reliable data on the logDow is available, the API is coloured light grey. Two theoretical distributions are fit (normal distribution based on either log10 or on Box–Cox-transformed dataset). The fitted distribution and calculated 5 % and 1 % NOECs are marked in blue (log10) and red (Box–Cox). The 95 % confidence interval (CI) for the “Box–Cox” model is shown as dashed black line. The 1 % and 5 % level are depicted as dashed grey lines. Figure S11. Overview on the total system DT50 (12 °C) of 196 APIs, sorted by pharmaceutical group. Bold lines depict the median, boxes the 25 % and 75 % percentiles, whiskers the 1.5 interquantile ranges. Each black dot represents a single API. The criteria for classification as “persistent” (DT50 ≥ 120 d) and “very persistent” (DT50 ≥ 180 d) are illustrated in blue and red, respectively. A detailed description of the pharmaceutical groups is given in Table S1. Table S1. Description of the pharmaceutical groups and the respective substances, which are categorised in these groups. Table S2. Metrics and results of fitted theoretical distributions for API effect concentrations (NOEC/EC10). Two different datasets were explored: the full dataset and an adjusted dataset excluding endocrine-active substances and antiparasitics. Two different models were chosen: a normal distribution fitted to the Box–Cox-transformed dataset, and a normal distribution fitted to a log10-transformed dataset. The depicted model metrics are based on the transformed data, 5 % and 1 % NOECs/percentiles and confidence intervals are backtransformed. AICs are not directly comparable between models, because both are based on differently transformed datasets. Table S3. Percentiles of total system DT50 (12 °C) of 196 APIs displayed in Figure 3. Data originated from OECD 308 “Aerobic and Anaerobic Transformation in Aquatic Sediment Systems” studies. DT50 values higher than 100 d are extrapolated. Table S4. Maximum concentrations of APIs in sewage sludge, reported in publicly available literature. Table S5. Combined trigger values Koc and PECsw for substances entering a risk assessment for soil organisms and their corresponding values as Fstp*_sludge, DOSEAS, Elocal and PECsoil. Table S6. List of substances with at least one valid aquatic NOEC/EC10 available. The respective pharmaceutical group (explained in Table S1) is indicated for each substance. The column “effect data” describes whether aquatic (A) and/or terrestrial (T) effect data were available. When data were available for all three organism groups, this is indicated by (3). The columns “Water–sediment simulation data” and “Koc data” indicate whether reliable half-lives from OECD308, and reliable adsorption coefficient data were available. All substances with aquatic effect data were included in the “full dataset”, endocrine-active substances and antiparasitics were excluded from the “adjusted dataset”, which was used for the derivation of an aquatic PEC action limit. The last column indicates whether the API was also evaluated in the publication of Gunnarsson et al. (2019) and if the same lowest aquatic NOEC was used (=) or not (≠). (PDF 1378 KB)