The global practice of reusing sewage sludge in agriculture
and
its landfill disposal reintroduces environmental contaminants, posing
risks to human and ecological health. This study screened sewage sludge
from 30 Chinese cities for androgen receptor (AR) disruptors, utilizing
a disruptor list from the Toxicology in the 21st Century program (Tox21),
and identified 25 agonists and 33 antagonists across diverse use categories.
Predominantly, natural products 5α-dihydrotestosterone and thymidine
emerged as agonists, whereas the industrial intermediate caprolactam
was the principal antagonist. In-house bioassays for identified disruptors
displayed good alignment with Tox21 potency data, validating employing
Tox21 toxicity data for theoretical toxicity estimations. Potency
calculations revealed 5α-dihydrotestosterone and two pharmaceuticals
(17β-trenbolone and testosterone isocaproate) as the most potent
AR agonists and three dyes (rhodamine 6G, Victoria blue BO, and gentian
violet) as antagonists. Theoretical effect contribution evaluations
prioritized 5α-dihydrotestosterone and testosterone isocaproate
as high-risk AR agonists and caprolactam, rhodamine 6G, and 8-hydroxyquinoline
(as a biocide and a preservative) as key antagonists. Notably, 16
agonists and 20 antagonists were newly reported in the sludge, many
exhibiting significant detection frequencies, concentrations, and/or
toxicities, demanding future scrutiny. Our study presents an efficient
strategy for estimating environmental sample toxicity and identifying
key toxicants, thereby supporting the development of appropriate sludge
management strategies.