Table 3 Chemical identification of the metabolic features associated with phthalate exposure in the metabolic-wide association study at visit 1 (n = 216) and visit 2 (n = 145) after correction for multiple testing (q < 0.2) using generalized linear models

From: Impact of prenatal phthalate exposure on newborn metabolome and infant neurodevelopment

m/z

rt

Ontology level*

Metabolite

Exposure

Association with exposure (β)

Pathways

Biological function

Visit 1 (8–14 weeks) n = 216

181.0733

1.62

OL2a

Tyrosine

MBP

−0.0046

Tyrosine metabolism (endogenous)

Thyroid function72; neurotransmitter production22

211.0844

2.86

OL2a

2-amino-3-(4-hydroxy-3-methoxyphenyl) propanoic acid

MBP

0.0030

Pharmaceutical (foodome)

Not enough information

178.0496

3.97

OL2a

3-Hydroxyhippuric acid

MBP

0.0012

Microbial metabolite (foodome)

Not enough information

174.0549

6.39

OL2b

Quinaldic acid

MBP

0.0031

Tryptophan metabolism (endogenous)

Not enough information

243.1491

7.45

OL1

Tiglylcarnitine

MBP

0.0049

Acyl carnitine metabolism (endogenous)

Not enough information

234.0778

6

OL2a

(R)-N-Acetyl-S-(1-(hydroxymethyl)-2-propen-1-yl)-L-cysteine

MBP

−0.0032

Acrylamide metabolite (environmental)

Acrylamide is classified as a possible human carcinogen; found in cigarettes or processed foods32

105.0335

6.69

OL1

4-hydroxybenzaldehyde

MBP

0.0033

Biosynthesis of phenyl-propanoids (endogenous)

Promotes antiparasitic host response73

88.0393

2.71

OL2b

Serine

MBP

0.0021

Glycine, serine and threonine metabolism (endogenous)

Neurotransmitter precursor23

289.2523

16.54

OL2a

Dihomo-gamma-linolenic acid

MBP

−0.0012

Linoleic acid metabolism (endogenous)

Neural membrane phospholipid26

330.2554

13.25

OL2b

Docosapentaenoic acid

MBP

−0.0009

Fatty acid (endogenous)

Anti-inflammatory; found in high concentrations in breastmilk74

243.1127

7.6

OL2a

Oxadixyl

MBP

−0.0022

Fungicide used in food crops (environmental)

Not enough information

215.1178

11.1

OL2a

Melatonin

MBP

0.0059

Circadian entrainment (endogenous)

Anti-oxidative effects in newborns75

190.1073

8.53

OL2a

2-Octenedioic acid

MBP

−0.0018

Fatty acid (endogenous)

Not enough information

360.2741

11.69

OL1

3-hydroxydodecanoyl carnitine

MBP

−0.0019

Acyl carnitine metabolism (endogenous)

Related to fatty acid oxidation and energy metabolism76

193.0737

4.28

OL2b

3-Methylhippuric acid

MBP

0.0014

Xylene metabolite (environmental)

Xylenes are often used as solvents in household products77

777.6937

11.82

OL1

Thyroxine

MBP

−0.0011

Tyrosine metabolism (endogenous)

Thyroid hormone; low level associated with increased illness and neurodevelopmental issues in newborns25

259.1073

8.58

OL2a

Linagliptin

MBP

−0.0014

Dipeptidyl peptidase-4 (DPP-4) inhibitor (drug)

Lowers blood sugar in patients by signaling the liver to stop producing glucose78

193.0972

1.55

OL1

Trans-3’-Hydroxycotinine

MBP

0.0048

Nicotine metabolite (endogenous)

Indicator of exposure to cigarette smoke; inversely associated with birth weight31

157.0608

3.3

OL2b

Formiminoglutamic acid

MBP

0.0023

Folate bioavailability (foodome)

Metabolite accumulates with inadequate availability of folate; used as a biomarker of folate deficiency79

197.0185

4.86

OL2a

hydroxyphenylacetic acid

MBP

0.0022

Tyrosine metabolism (endogenous)

Not enough information

308.0908

8.35

OL2b

Glutathione reduced

MBP

0.0017

Glycine, serine and threonine metabolism (endogenous)

Prevents oxidative stress80

156.1019

5.87

OL2b

Acetylleucine

MEHP

0.0061

Valine, leucine and isoleucine metabolism (endogenous)

Decreased neural inflammation in mouse models81

199.0962

7.23

OL2a

Phenyllactic acid

MEHP

−0.0057

Phenylalanine metabolism (endogenous)

Not enough information

273.1844

10.95

OL2a

Estradiol-17alpha

MEHP

0.0080

Steroid hormone biosynthesis (endogenous)

Reduced chronic inflammation in mouse models82

Visit 2 (24–30 weeks) n = 145

292.2348

16.08

OL2a

11-Octadecen-9-ynoic acid

MBP

−0.0113

Fatty acid (endogenous)

Not enough information

237.1232

4.38

OL2a

Tryptophan

MECPP

0.0044

Tryptophan metabolism (endogenous)

Essential to brain development and the establishment of sleep-wake cycles in newborns24

218.1386

5.74

OL2a

15-Valerolactone

MECPP

−0.0039

Not enough information (endogenous)

Not enough information

199.1076

8.63

OL2a

Tyrosine

MECPP

−0.0063

Tyrosine metabolism (endogenous)

Thyroid function72; Neurotransmitter production22

266.136

7.83

OL2a

5-methyl-1,3-benzenediol

MECPP, MEOHP

0.0058, 0.0100

Not enough information (foodome)

Not enough information

156.1019

5.87

OL2b

Acetylleucine

MECPP, MEOHP

0.0029, 0.0055

Valine, leucine and isoleucine metabolism (endogenous)

Decreased neural inflammation in mouse models81

  1. MEP monoethyl phthalate, MBP mono-n-butyl phthalate, MiBP monoisobutyl phthalate, MBzP monobenzyl phthalate, MEHP mono-2-ethylhexyl phthalate, MEOHP mono-2-ethyl-5-oxohexyl phthalate, MEHHP mono-2-ethyl-5-hydroxyhexyl phthalate, MECPP mono-2-ethly-5-carboxypentyl phthalate, \(\Sigma\)DEHP Sum of Di-2-ethylhexyl phthalate metabolites.
  2. *Ontology level indicates the strength of the evidence supporting each metabolite’s identification or annotation, considering retention time, exact mass (MS), MS/MS fragmentation pattern, and isotopic ion pattern. Metabolites that closely matched the IESL by RT (within ±0.5 min), MS (within <5 ppm), and displayed a high degree of similarity in MS/MS fragmentation patterns (similarity score >30) received an OL1 label. For metabolites matching by RT and MS, they were labeled OL2a. An OL2b label was assigned to signals that matched the IESL by MS and MS/MS but fell outside the RT window (±0.5 min).
  3. The chemical identity was conducted by matching peaks by accurate mass and retention time to authentic reference standards in an in-house library run under identical conditions using tandem mass spectrometry. Source data and exact two-sided p-values are provided as a Source Data file. Atlanta African American Maternal–Child cohort, 2016–2018.
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