Improving biological measurements to determine chemical exposure in occupational and wildlife toxicology.

摘要

This dissertation focuses on improving measurements to assess exposures to environmental contaminants in occupational and wildlife toxicology. The two biomarkers studied are cholinesterases (ChEs) and Cytochrome P4501A (CYP1A).; In California, monitoring is required of blood (ChEs) for mixer-loaders and applicators working with organophosphate (OP) pesticides. Decreases in blood ChEs signal exposure has occurred. Previous work found that clinical laboratories were not measuring ChEs with optimized assays, leading to changes in the state regulations for ChE testing. Assisting clinical laboratories with meeting these requirements at the behest of the state resulted in twelve clinical laboratories being approved to continue with testing. An Ellman reference value for RBC AChE (8.11 +/- 0.92 SD umol/min/mL) was established by deriving a conversion factor between the Ellman and delta pH assay permitting use of the extensive database of the Cholinesterase Reference Laboratory of the Department of Defense. This reference value could be used to estimate the degree of inhibition associated with anticholinergic agents when baselines for individual subjects are lacking. Future applications include establishment of national standardized protocols and proficiency testing for clinical laboratories.; The second biomarker area concerns using CYP1A to assess the impact of polycyclic aromatic hydrocarbons (PAHs) on the decline in Steller's eiders (STEI-Polystitica stelleri) populations in North America working with the United States Geological Survey (USGS). CYP1A was measured using the ethoxyresorufin-O-deethylase (EROD) assay. Avian embryos exposed to beta-naphthoflavone (BNF), a known CYP1A inducer, were used as positive controls. Mean EROD activates were 25 fold higher with BNF treated compared to controls. Liver biopsies collected in the field by the USGS showed STEI EROD activity ranged from 4.64--412 pmol/min/mg protein, and Harelquin ducks (Histrionicus histrionicus) activity ranged from 20--688 pmol/min/mg protein. STEI held captive and exposed to BNF were induced four-fold compared to controls. The relationship between CYP1A activity and levels of chemical residuals collected from plasma of sea birds and their prey is under investigation by the USGS.