Plasticizers, due to the widespread
use of plastics, occur ubiquitously
in the environment. The reuse of waste resources (e.g., treated wastewater,
biosolids, animal waste) and other practices (e.g., plastic mulching)
introduce phthalates into agroecosystems. As a detoxification mechanism,
plants are known to convert phthalates to polar monophthalates after
uptake, which are followed by further transformations, including conjugation
with endogenous biomolecules. The objective of this study was 2-fold:
to obtain a complete metabolic picture of the widely used di-n-butyl phthalate (DnBP) by using a suite of complementary
techniques, including stable isotope labeling, 14C tracing,
and high-resolution mass spectrometry, and to determine if conjugates
are deconjugated in human microsomes to release bioactive metabolites.
In Arabidopsis thaliana cells, the
primary initial metabolite of DnBP was mono-n-butyl
phthalate (MnBP), and MnBP was rapidly metabolized via hydroxylation,
carboxylation, glycosylation, and malonylation to seven transformation
products. One of the conjugates, MnBP-acyl-β-d-glucoside
(MnBP-Glu), was incubated in human liver (HLM) and intestinal (HIM)
microsomes and was found to undergo rapid transformations. Approximately
15% and 10% of MnBP-Glu were deconjugated to the free form MnBP in
HIM and HLM, respectively. These findings highlight that phthalates,
as diesters, are susceptible to hydrolysis to form monoesters that
can be readily conjugated via a phase II metabolism in plants. Conjugates
may be deconjugated to release bioactive compounds after human ingestion.
Therefore, an accurate assessment of the dietary exposure of phthalates
and other contaminants must consider plant metabolites, especially
including conjugates, to better predict their potential environmental
and human health risks.
