Innovative Research for a Sustainable Future www.epa.gov/research ORCID: 0000-0002-4024-534X John Wambaugh l wambaugh.john@epa.gov l 919-451-5400 Product Deformulation to Identify Exposure Pathways for ToxCast Chemicals John Wambaugh1, Alice Yau2, Katherine Phillips3,4, Kristin A. Favela2, Chantel Nicolas1,4, Derya Biryol3,4, Christopher Grulke1,5, Ann M. Richard1, Paul Price3, Antony Williams1, Kristin Isaacs3, Russell Thomas1 National Center for Computational Toxicology1 and National Exposure Research Laboratory3, U.S. Environmental Protection Agency, Office of Research and Development Southwest Research Institute2, Oak Ridge Institute for Science and Education4, Lockheed Martin5 Abstract Introduction Results Estrogen Actives and Flame Retardants Summary High throughput screening (HTS) data that characterize chemically induced biological activity have been generated for thousands of chemicals by the US interagency Tox21 and the US EPA ToxCast programs. In many cases there are no data available for comparing bioactivity from HTS with relevant human exposures. The EPA’s ExpoCast program is developing high-throughput approaches to generate the needed exposure estimates using existing databases and new, high-throughput measurements. The exposure pathway (i.e., the route of chemical from manufacture to human intake) significantly impacts the level of exposure. The presence, concentration, and formulation of chemicals in consumer products and articles of commerce (e.g., clothing) can therefore provide critical information for estimating risk. We have found that there are only limited data available on the chemical constituents (e.g., flame retardants, plasticizers) within most articles of commerce. Furthermore, the presence of some chemicals in otherwise well characterized products may be due to product packaging. We are analyzing sample consumer products using 2D gas chromatograph (GC) x GC Time of Flight Mass Spectrometry (GCxGCTOF/MS), which is suited for forensic investigation of chemicals in complex matrices (including toys, cleaners, and food). In parallel, we are working to create a reference library of retention times and spectral information for the entire Tox21 chemical library. In an examination of five plastic children’s toys, as many as 114 and as few as 56 chemicals were identified in each toy, with between 0 and 40 unidentified chemicals in each. Putative endocrine disrupter, Bisphenol A (BPA), was identified as present in a product marked “BPA free”. Information on chemical constituents of products, while only a prerequisite to actual exposure, provides heuristics for estimating likely human exposure pathways for thousands of chemicals. Methods Example: Chromatograms for Baby Toys [solvent tail] is is is is is s s s s s s s is [solvent tail] is is is is is s s s s s s s is [Column bleed] [solvent tail] [Column bleed] is is is is is is s s s s s s s [solvent tail] [Column bleed] is is is is is is s s s s s s s [solvent tail] [Column bleed] is is is is is is s s s s s s s [solvent tail] [Column bleed] is is is is is is s s s s s s s [solvent tail] [Column bleed] is is is is is is s s s s s s s [solvent tail] [Column bleed] is is is is is is s s s s s s s [solvent tail] [Column bleed] is is is is is is s s s s s s s [solvent tail] [Column bleed] is is is is is is s s s s s s s [solvent tail] [Column bleed] is is is is is is s s s s s s s [solvent tail] [Column bleed] is is is is is is s s s s s s s is = internal standard s = surrogate Product 1 Product 2 Product 3 Product 4 Product 5 Retention Time First Dimension (s) Retention Time Second Dimension (s) 100x 10x 1x DCM Dilution • Southwest Research Institute conducted analytical chemistry screening for large numbers of chemicals in consumer products and articles of commerce • Five sample products were arbitrarily selected from each of twenty different categories • Products were analyzed using two dimensional gas chromatograph (GC) x GC Time of Flight Mass Spectrometry