Epidemiology-based wastewater monitoring for ecological risks of anti-tuberculosis drugs mixture effects

First-line anti-tuberculosis (TB) drugs are commonly used to treat TB worldwide, leading to more contaminated wastewater being widely discharged into aquatic environments. However, studies of mixture interactions of anti-TB drugs and their residues in aquatic environments are scarce. This study aime...

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Bibliographic Details
Published in:The Science of the total environment 2023-09, Vol.892, p.164560-164560, Article 164560
Main Authors: Chen, Wei-Yu, Chen, Yi-Fang, Tsai, Jer-Min, Huang, Hsin-Mei, Su, Yong-Chao
Format: Article
Language:English
Subjects:
Anti-tuberculosis drugs
Antitubercular Agents - therapeutic use
Daphnia magna
Ecotoxicological risk
Epidemic models
Ethambutol - therapeutic use
Isoniazid - therapeutic use
Mixture toxicity
Rifampin - therapeutic use
Wastewater
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Summary:First-line anti-tuberculosis (TB) drugs are commonly used to treat TB worldwide, leading to more contaminated wastewater being widely discharged into aquatic environments. However, studies of mixture interactions of anti-TB drugs and their residues in aquatic environments are scarce. This study aimed to determine the toxic interactions of anti-TB drugs—isoniazid (INH), rifampicin (RMP), and ethambutol (EMB)—in binary and ternary mixtures on Daphnia magna and used the epidemiology of TB history to construct epidemiology-based wastewater monitoring for assessing the environmental release of residues and related ecological risks. The acute immobilization of median effect concentrations (EC50) was 25.6 mg L−1 for INH, 80.9 mg L−1 for RMP, and 188.8 mg L−1 for EMB, as toxic units (TUs) for assessing mixture toxicity. The ternary mixture exhibited the lowest TUs at 50 % effects with 1.12, followed by 1.28 for RMP + EMB, 1.54 for INH + RMP, and 1.93 for INH + EMB, indicating antagonistic interactions. Nevertheless, the combination index (CBI) was used to examine the mixture toxicity in response to immobilization, revealing that the ternary mixture of CBI ranged from 1.01 to 1.08, tending to have a nearly additive effect when suffering >50 % effect (at high concentration levels). The forecasted environmentally relevant concentrations of anti-TB drugs have been on downward trends with ng L−1 level from 2020 to 2030 in Kaohsiung, Taiwan. Although ecotoxicological risks from the wastewater treatment plant and receiving water in the field were slightly greater than the prediction from epidemiology-based wastewater monitoring, there were no risk concerns. Here, we achieved the establishment of evidence that anti-TB drug mixtures' interaction and epidemiological-based monitoring support a systematic approach, resolving the absence of the mixture toxicity information for anti-TB mixture risk assessment in aquatic environments. [Display omitted] •Binary anti-TB drug mixtures exhibited antagonistic interactions.•Ternary anti-TB drug mixture tended to be antagonistic and nearly had an additive effect.•Concentration of anti-TB drugs was estimated from epidemiology-based wastewater monitoring.•There were no ecological risk concerns in anti-TB drug mixtures.
ISSN:0048-9697
1879-1026
DOI:10.1016/j.scitotenv.2023.164560