Table 2.

Exogenous Metabolites Identified in Seminal Plasma via Match against the NC HHEAR Hub In-house Physical Standard Library within MS, RT, and MS/MS

aCompound Name	b Ontology	c Source of Exposure	Structure category
styrene	OL1, OL2b	Environmental	Benzene metabolite
3,5-Di-tert-butyl-4-hydroxybenzaldehyde	OL1	Environmental	BHA metabolite
1,3-xylene	OL1, OL2b (3)	Environmental	Dimethylbenzene
9-Hydroxyfluorene	OL1, OL2a	Environmental	Fluorene
Oxybenzone	OL1	Environmental	Oxybenzone
Mono-(2-ethylhexyl) Terephtalate	OL1	Environmental	Phthalate
Mono-n-octyl phthalate	OL1	Environmental	Phthalate
Mono-2-ethylHydroxyhexyl Terephthalate (MEHHTP)	OL1, OL2a	Environmental	Phthalate
Monoisobutyl phthalic acid	OL1, OL2a	Environmental	Phthalate
Butyl benzyl phthalate	OL1, OL2b	Environmental	Phthalate
Cotinine	OL1	Environmental	Tobacoo metabolite
4-hydroxy-3-methoxybenzaldehyde	OL1	Ingested food	Benzaldehyde
4-Hydroxyhippuric acid	OL1 (2), OL2b	Ingested food	Hippuric acid and derivatives
1,3-dimethyluric acid	OL1	Ingested food	Purine derivatives
1,3-dimethylxanthine	OL1	Ingested food	Purine derivatives
1,7-dimethylxanthine	OL1	Ingested food	Purine derivatives
7-methylxanthine	OL1	Ingested food	Purine derivatives
Caffeine	OL1	Ingested food	Purine derivatives
1-methylxanthine	OL1, OL2a	Ingested food	Purine derivatives
3,7-dimethylxanthine	OL1, OL2a	Ingested food	Purine derivatives
4-pyridoxic acid	OL1	Ingested food	Pyridinecarboxylic acids
1-methyl-3-pyridiniumcarboxylic acid	OL1	Ingested food	Pyridinecarboxylic acids
indole-3-acetic acid	OL1, OL2b	Ingested food	Tryptophan-indole derivatives
Acetaminophen	OL1 (2)	Med/Drug	Analgesic
Naproxen	OL1	Med/Drug	Nonsteroidal anti-inflammatory drug
Carboxyibuprofen	OL1, OL2a	Med/Drug	Nonsteroidal anti-inflammatory drug metabolite
leucyl-proline	OL1, OL2a(2)	Microbiome	Dipeptide
N-Acetylglucosamine	OL1, OL2a, OL2b(2)	Microbiome	Sugar amide
Indolepropionate	OL1	Microbiome	Tryptophan-indole derivatives
4-Hydroxyphenyllactate	OL1, OL2a	Microbiome	Tyrosine metabolite

^aTable 2 lists the most confident (OL1) exogenous metabolites identified from seminal plasma via matching against the NC HHEAR Hub In-house physical standard library (IPSL). The assigned compound name is based on the name of the reference standards run on the UHPLC-HRMS platform, and some of the isomers (e.g., D, L isomers or R, S isomers) may not be differentiated.

^bOntology levels: OL1, highly confident identification based on matching with IPSL via retention time (RT, with RT error≤|0.5|), exact mass (MS, with mass error<5ppm), and tandem mass similarity (MS/MS, with similarity ≥30); OL2a, confident identification based on matching with IPSL via MS and RT; OL2b, annotations for the isomer or derivatives of the compound listed but not the compound itself, based on matching with IPSL via MS and MS/MS. In situations where multiple peaks correspond to a compound via OL1 and (or) OL2a, it may indicate closely eluting isomers or the presence of split peaks and also means high confidence that the assigned compound exists within the biological sample, even if it is unclear which of the multiple peaks best represented that compound. In situations where one or multiple peaks match to a compound via level 2b, it indicates the presence of derivative(s), isomer(s), or conjugate(s) related to the matched compound.

^cThe source of exposure indicates the possible sources where the exogenous parent compounds, or their metabolites derived in the human body after the exposure, might be originated. One exogenous compound or metabolites might originate from multiple sources. Identification and annotation of other exogenous metabolites within less confident levels (OL2 and OL2b) were shown in table S1.