This dissertation examines the ability of in vitro biotransformation assays to provide an indication of metabolic potential. The potential for xenobiotic compounds to bioconcentrate in aquatic organisms is expressed through the bioconcentration factor (BCF). The metabolic loss of ibuprofen, norethindrone and propranolol was measured using rainbow trout (Oncorhynchus mykiss) and channel catfish (Ictalurus punctatus) gill and liver S9 fractions, microsomes and cell suspensions. Metabolic transformation rates (kM) were extrapolated from in vitro intrinsic clearance of parent compound (CLm) and integrated into a refined BCF model. In general, CLm of test compounds was greater in liver S9 fractions and hepatocytes. However, the influence of hepatic metabolism on kM and BCF was limited by hepatic blood flow (20-25%) compared to gill blood flow (~100%). A significant difference was noted between BCF solely based on KOW and BCF including kM. These studies indicate that the inclusion of kM in BCF models can bring predicted bioconcentration estimates closer to in vivo values. Primary cell suspensions are preferred over subcellular fractions as cell suspensions possess both phase I and phase II enzyme activity. Further study was conducted on ibuprofen biotransformation pathways. As fish do not contain the same cytochrome P450 (CYP) 2C homologs known to …

The primary objective of this work was to determine the tissue-specific bioconcentration factors (BCFs) of the selected pharmaceuticals: norethindrone (NET), ibuprofen (IBU), verapamil (VER), clozapine (CLZ) and fenofibrate (FFB) in two freshwater fishes: fathead minnow and channel catfish. BCF tests on fathead followed the standard OECD 42-day test while a 14-day abridged test design was used in catfish exposures. Additional objectives included a) comparing the measured BCFs to the US EPA's BCFWIN model predicted values, b) comparing the BCF results from the standard and reduced tests, and c) prediction of chronic risk of the pharmaceuticals in fish using the human therapeutic plasma concentrations. Each test included uptake and depuration phases to measure tissue-specific kinetic BCFs. The results indicated that all the pharmaceuticals, except IBU, have the potential for accumulation in fish. Estimated BCFs for NET, VER and FFB may not be significant in view of the current regulatory trigger level (BCF ≥ 2000); however, CLZ's BCF in the liver had approached the criterion level. Significant differences were noticed in the tissue-specific uptake levels of the pharmaceuticals with the following general trend: (liver/kidney) > (gill/brain) > (heart/muscle) > plasma. IBU uptake was highest in the plasma. When compared to the measured …

Northern bobwhite populations have declined concurrent with global warming. The focal period of this study was the 12-d pre-incubation period, when bobwhite eggs remain in the nest without the thermal protection of the incubating parent. This study first established the storage and thermal limits of bobwhite eggs, then investigated how global warming may impact oviparous embryos and how bobwhite embryos react to acute and chronic doses of simulated drought temperatures during pre-incubation. First, the maximum storage limit of bobwhite eggs was determined by storing eggs ≤21 d and measuring hatching success and pH of egg albumen and yolk. Hatching success of stored eggs declined after 14 d, when yolk and albumen pH reached levels detrimental to embryonic development. Secondly, thermal limits were determined by exposing bobwhite eggs to hyperthermic temperatures (38-52 °C). Bobwhite embryos survived 50 °C for 1 h, 49 °C for 3 h and 46 °C for 6 h. Results indicate an adaptation to the naturally occurring temperature extremes that can occur in the bobwhite's southern range during pre-incubation. Subsequently, bobwhite eggs were exposed to either low constant (LC), low fluctuating (LF), high constant (HC), or high fluctuating (HF) temperatures during pre-incubation to determine if the nature of …