Grouping of Petroleum Substances as Example UVCBs by Ion Mobility-Mass Spectrometry to Enable Chemical Composition-Based Read-Across.

Substances of Unknown or Variable composition, Complex reaction products, and Biological materials (UVCBs), including many refined petroleum products, present a major challenge in regulatory submissions under the EU Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and US High Production Volume regulatory regimes. The inherent complexity of these substances, as well as variability in composition obfuscates detailed chemical characterization of each individual substance and their grouping for human and environmental health evaluation through read-across. In this study, we applied ion mobility mass spectrometry in conjunction with cheminformatics-based data integration and visualization to derive substance-specific signatures based on the distribution and abundance of various heteroatom classes.

A chemical-biological similarity-based grouping of complex substances as a prototype approach for evaluating chemical alternatives.

Comparative assessment of potential human health impacts is a critical step in evaluating both chemical alternatives and existing products on the market. Most alternatives assessments are conducted on a chemical-by-chemical basis and it is seldom acknowledged that humans are exposed to complex products, not individual substances. Indeed, substances of nknown or ariable composition, omplex reaction products, and iological materials (UVCBs) are ubiquitous in commerce yet they present a major challenge for registration and health assessments.

Large-conductance Ca2+-dependent K+ channels regulate basal uteroplacental blood flow in ovine pregnancy.

Objectives: The mechanisms regulating basal uteroplacental blood flow (UBF) and the greater than 30-fold increase observed in normal pregnancy remain unclear. Although vascular growth contributes in early gestation, vasodilation accounts for the exponential rise seen in the last third of pregnancy. Large conductance potassium channels (BK(Ca)) are expressed in uterine vascular smooth muscle (VSM), but the extent of their role in regulating UBF in pregnancy is unclear.

Estrogen selectively up-regulates eNOS and nNOS in reproductive arteries by transcriptional mechanisms.

Objective: To determine the mechanism(s) whereby daily and acute estradiol-17beta (E(2)beta) exposure modifies endothelium-derived nitric oxide synthase (eNOS) and vascular smooth muscle (VSM) neuronal nitric oxide synthase (nNOS) in reproductive and nonreproductive arteries and to localize NOS isoform expression within the vessel wall.

Methods: Oophorectomized nonpregnant ewes received E(2)beta (1 microg/kg per day) or no E(2)beta for 5-6 days or acute E(2)beta (1 microg/kg) on day 6-7 with or without daily E(2)beta. Uterine, mammary, mesenteric, and femoral arteries were collected at completion of each study, adventitia were removed, and samples were frozen and stored at -80C.