Temporal biomonitoring studies can assess changes in population exposures to contaminants, but collection of biological specimens with adequate representation and sufficient temporal resolution can be resource-intensive. Newborn Screening Programs (NSPs) collect blood as dried spots on filter paper from nearly all infants born in the United States (U.S.). In this study, we investigated the use of NSP blood spots for temporal biomonitoring by analyzing perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in 110 New York State (NYS) NSP blood spot composite specimens collected between 1997 and 2007, representing a total of 2640 infants. All analytes were detected in g90% of the specimens. Concentrations of PFOS, PFOSA, PFHxS, and PFOA exhibited significant exponential declines after the year 2000, coinciding with the phase-out in PFOS production in the U.S. Calculated disappearance half-lives for PFOS, PFHxS, and PFOA (4.4, 8.2, and 4.1 years, respectively) were similar to biological half-lives reported for retired fluorochemical workers. Our results suggest sharp decreases in perinatal exposure of NYS infants to PFOS, PFOSA, PFHxS, and PFOA and demonstrate, for the first time, the utility of NSP blood spots for assessment of temporal trends in exposure.

Cyanide (CN) is a ubiquitous environmental toxicant. The measurement of CN in whole blood is a common exposure assay, but values are error prone because of CN's rapid metabolism and clearance (t1/2 < 1 h) from this compartment. This study was undertaken to determine whether CN forms covalent adduct(s) with plasma proteins that could serve as stable biomarker(s) and potential surrogate(s) of exposure. When added to human blood, plasma, or serum, CN formed covalent adducts with immunoglobulin G (IgG) and serum albumin (HSA) in the plasma fraction. Covalent adducts were not detected in the cellular, primarily erythrocyte, fraction. With human, mouse, and rabbit IgGs, the reaction with CN occurred at intra- and/or interchain disulfide linkages in the heavy and light chains. Digestion of CN-treated HSA with trypsin or the endoproteinase Lys-C at basic pH produced tautomeric 2-iminothiazoline-4-carboxylyl/2-aminothiazolidine-4-carboxylyl (itcCys) N-terminal peptides exclusively, consistent with prior model peptide/protein studies showing that under basic conditions internal S-cyanylated-Cys residues cyclize with concomitant release of the upstream peptide. The most readily detectable reaction of CN with purified HSA was at Cys34, the only Cys of the 35 present not connected as internal cystines. Because CN does not react with free sulfhydryl groups, it is probable that S-cyanylation at Cys34 occurs at those residues that carry GSH, Cys, or other small molecules as mixed disulfides. Relatively less detectable, modified Cys residues were also identified at positions 53, 124, 392, 477, and 487. When 14CN was added to human serum or whole blood at concentrations spanning a putative nontoxic to lethal range, stable adduct formation with HSA occurred in a linear, concentration-dependent reaction that was complete within 2 h. These attributes of the reaction, coupled with a plasma compartment location, suggest that quantitation of CN bound to HSA would provide a much more reliable assessment of exposure than does measurement of CN in blood.