The global spread of antimicrobial resistance (AMR) is
concerning
for the health of humans, animals, and the environment in a One Health
perspective. Assessments of AMR and associated environmental hazards
mostly focus on antimicrobial parent compounds, while largely overlooking
their transformation products (TPs). This review lists antimicrobial
TPs identified in surface water environments and examines their potential
for AMR promotion, ecological risk, as well as human health and environmental
hazards usingin silicomodels. Our review also summarizes
the key transformation compartments of TPs, related pathways for TPs
reaching surface waters and methodologies for studying the fate of
TPs. The 56 antimicrobial TPs covered by the review were prioritized
via scoring and ranking of various risk and hazard parameters. Most
data on occurrences to date have been reported in Europe, while little
is known about antibiotic TPs in Africa, Central and South America,
Asia, and Oceania. Occurrence data on antiviral TPs and other antibacterial
TPs are even scarcer. We propose evaluation of structural similarity
between parent compounds and TPs for TP risk assessment. We predicted
a risk of AMR for 13 TPs, especially TPs of tetracyclines and macrolides.
We estimated the ecotoxicological effect concentrations of TPs from
the experimental effect data of the parent chemical for bacteria,
algae and water fleas, scaled by potency differences predicted by
quantitative structure–activity relationships (QSARs) for baseline
toxicity and a scaling factor for structural similarity. Inclusion
of TPs in mixtures with their parent increased the ecological risk
quotient over the threshold of one for 7 of the 24 antimicrobials
included in this analysis, while only one parent had a risk quotient
above one. Thirteen TPs, from which 6 were macrolide TPs, posed a
risk to at least one of the three tested species. There were 12/21
TPs identified that are likely to exhibit a similar or higher level
of mutagenicity/carcinogenicity, respectively, than their parent compound,
with tetracycline TPs often showing increased mutagenicity. Most TPs
with increased carcinogenicity belonged to sulfonamides. Most of the
TPs were predicted to be mobile but not bioaccumulative, and 14 were
predicted to be persistent. The six highest-priority TPs originated
from the tetracycline antibiotic family and antivirals. This review,
and in particular our ranking of antimicrobial TPs of concern, can
support authorities in planning related intervention strategies and
source mitigation of antimicrobials toward a sustainable future.