We set out to determine whether infrared (IR) spectra of treated MCF-7 cells derived using attenuated total reflection Fourier-transform IR (ATR) microspectroscopy could be used to signature different exposures. Serum-lipid samples from residents living in an electronics waste (e-waste) dismantling region (Region E, n = 26) in the south of P.R. China or from a nearby region (Region S, n = 20) associated with the fishing industry were obtained. Following extraction, estrogen receptor-positive MCF-7 cells were treated for 24 h with ≤5-mg lipid equivalent of individual extracts prior to ethanol fixation; subsequently, IR spectra of treated-cell populations were obtained using ATR microspectroscopy. Levels of organochlorinated and brominated compounds in parallel extracts were also determined. Principal component analysis (PCA) was employed to ascertain whether IR-spectral scores would cluster according to particular cohort. Scores plots following PCA highlighted significant clustering dependent on with which set of extracts MCF-7 cells were treated. This suggests marked differences in the cell-biochemical modulating effects induced by either set of extracts. Analysis of contaminant profiles in the extracts showed that polybrominated diphenyl ethers (PBDEs) accounted for 46.0% of total organohalogens and were higher than dichloro-diphenyl-trichloroethanes (DDTs) in Region E; DDTs were the major contaminants (85.2% of total contaminant load) compared to PBDEs (8.7%) in Region S. These results suggest that ATR microspectroscopy can segregate cell-biochemical effects as a consequence of very different exposure paradigms.