OPS 20: Chemicals, biomarkers, omics, Room 110, Floor 1, August 27, 2019, 4:30 PM - 5:30 PM Background: Phthalates, ubiquitous chemicals used in many household and personal care products, act as endocrine disruptors interfering with normal child development. DNA methylation may be a mechanism involved as previous studies have linked prenatal exposure to altered DNA methylation in cord blood, but independent validation is necessary. Methods: We conducted a hypothesis-free epigenome-wide discovery of associations between prenatal phthalate exposure and cord blood DNA methylation in a pregnancy cohort in Mexico City (PROGRESS). Spot urine samples from mothers were collected at 2nd and 3rd trimester of pregnancy. Urinary concentrations of seven phthalate metabolites were quantified using high performance liquid chromatography tandem mass spectrometry. Metabolite concentrations were summarized and averaged between timepoints to estimate exposure to four common parent phthalate diesters: diethyl phthalate, di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), and di(2-ethylhexyl) phthalate. Concentrations of mono-n-butyl phthalate (a DnBP metabolite) were higher than seen in the United States but similar to other studies in Mexico. Umbilical cord blood samples were collected at delivery and assayed on the Infinium MethylationEPIC microarray querying methylation levels at 865,859 loci. Results: Data were available for 442 mother-child dyads. Out of the 4 × 865,859 potential associations screened using adjusted robust regression, 157 reached significance at a global false discovery rate of 15%, of which 19 loci formed 8 regions (as they were located within 10,000 base pairs of each other), or were associated with more than one phthalate diester. Regions overlapped several genes with expression almost exclusively in brain or testes: TMEM239 (×DnBP), FSTL5 (×BBzP, DnBP), EFNB3 (×DnBP), or STK32C (×DnBP). Conclusions: Our results add to the evidence that DNA methylation is a mechanism through which prenatal exposure to select phthalates might affect child development. Phthalates have been associated with neuro- and reproductive toxicity which is consistent with our findings.