Bruce A. Owen

Evaluation of the metabolism in rat hearts of two new radioiodinated 3-methyl-branched fatty acid myocardial imaging agents.

The biological fate of two new radioiodinated 3-methyl-branched fatty acids has been evaluated in rat hearts following intravenous administration. Methylbranching was introduced in [15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) and 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) to inhibit β-oxidation. The goals of these studies were to correlate the effects of methyl-branching on the incorporation of these agents into the various fatty acid pools and subcellular distribution profiles, and to relate these data to the myocardial retention properties. The properties of BMIPP and DMIPP were compared with the 15-(p-iodophenyl)pentadecanoic acid straight-chain analogue (IPP). Differences in the heart retention of the analogues after intravenous administration in rats correlated with differences observed in subcellular distribution patterns. The dimethyl DMIPP analogue showed the longest retention and the highest association with the mitochondrial and microsomal fractions (34%, 38%) 30 min after injection. These data are in contrast to the rapid clearance of the straight-chain IPP analogue which showed much lower relative association with the mitochondria and microsomes (18%, 15%). The distribution patterns of each analogue in the various lipid pools appeared consistent with the expected capacity of the analogues to be metabolized by β-oxidation. In contrast to the rapid oxidation of the straight-chain IPP analogue, the 3-monomethyl BMIPP analogue appeared to undergo slower oxidation and clearance, whereas the dimethyl-branched DMIPP analogue was apparently not catabolized by the myocardium. All three analogues showed some incorporation into triglycerides. The metabolism patterns of the branched analogues reported here may provide useful information in the description of the mechanisms by which BMIPP and DMIPP are retained in rat myocardium.

Formaldehyde in drinking water: comparative hazard evaluation and an approach to regulation.

Formaldehyde, a widely used industrial chemical to which humans are ubiquitously exposed, presented cause for concern when it was demonstrated to be carcinogenic in laboratory animals. Risk assessment protocols subsequently applied to formaldehyde are of questionable validity in light of the results of recent mechanistic investigations of biological responses to formaldehyde. Further, the hazard of ingested formaldehyde is not addressed in current assessment protocols. This paper addresses the potential human health risks accompanying low-level exposure to formaldehyde as a contaminant in drinking water. In this exposure scenario, noncarcinogenic risk from inhalation of formaldehyde from drinking water is evaluated through knowledge of the metabolism and biological effects of formaldehyde exposure. Noncarcinogenic risk from ingestion of formaldehyde in drinking water is evaluated from the perspective gained by comparison with dietary sources of formaldehyde. Carcinogenic risk to humans is evaluated in light of recent investigations into the mechanisms underlying biological responses to formaldehyde exposure. Finally, based on a comparison of ingestion of formaldehyde in drinking water with ingestion of naturally occurring formaldehyde in foods, a comparative hazard approach to formaldehyde regulation is offered as a supplement to the rigid evaluation protocols currently used.

Quantitation of Free-Living Amoebae and Bacterial Populations in Eyewash Stations Relative to Flushing Frequency

This study investigated the concentration of amoebic and bacterial populations in eyewash station water relative to various flushing regimens. Amoebae concentrations averaged approximately 200 amoebae/100 mL in 13 of 15 stations positive for amoebae and consisted of Hartmannella and Acanthamoeba. Bacterial concentrations ranged from 10(0) to more than 10(5) colony forming units per mL. Amoebic concentrations differed notably between stations located in Buildings X and Y (p < 0.0001). Further study indicated that removal of diffusing screens did not substantially change (p > 0.05) the concentration of amoeba. Amoebic and bacterial concentrations temporarily decreased with the various flushing regimens tested. Lower amoebic concentrations were not sustained by a weekly 3-minute or a monthly 1-minute flushing regimen. However, weekly 3-minute flushes appeared to be more effective in maintaining lowered bacterial concentrations (p < 0.0001).

Effects of fasting on the myocardial subcellular distribution and lipid distribution of terminal p-iodophenyl-substituted fatty acids in rats.

The myocardial lipid pool distribution and subcellular distribution of radiolabeled methyl-branched fatty acids in rats was evaluated under conditions of fasting (24 h) and feeding. With the unbranched iodophenyl fatty acid, fasting resulted in increased myocardial extraction and clearance time with a decrease in the incorporation into triglycerides and greater radioactivity in the mitochondrial fraction. With the monomethyl-branched analogue, the effects of fasting on lipid and subcellular distribution were minor except for a decrease in triglyceride incorporation. Like the unbranched analogue, the dimethyl-branched iodophenyl fatty acid showed increased myocardial extraction with fasting, however, this structurally-modified fatty acid showed increased rather than decreased incorporation into triglycerides.

Protection of human health from mixtures of radionuclides and chemicals in drinking water

This study was undertaken to develop a common scale for evaluating health risks from contaminated drinking water. For different agents, many unrealistic models of risk have been used. By intent, regulatory toxicology depends on “data-sparse, model-intensive” analogies from exotic animal genetics and novel exposures (NCRP 1989). The question is, does a risk evaluation so derived have any predictive validity? Absence of data prevents answer because regulatory toxicology rationalizes in step-by-step logic, which we callabsolute (i.e., predicts cases of disease in a population). Absolute models ensure safety, but do so at the cost of realism. In contrast, we makerelative comparisons in the manner of horsepower or RBE from radiation biology. All pollutants are assumed to contribute to toxic injury. Next, relative potencies are linked to the most credible standards. Thus, experience is transferred from well-studied chemicals to the new chemical by “data-intensive, model-sparse” methods. This logos provides much relative precision. Then, pollutants are compared with: (1) common foodstuffs, (2) ambient radiation background, or (3) utility-pure drinking water. Finally, an assessment is made for a waste disposal area.

Biotesting wastewater for hazard evaluation

Abstract Evaluation of the potential hazard of treated water can be performed in two basic ways: chemical identification followed by chemical-by-chemical hazard summation or by means of biotesting the water as if the contaminants were a single compound. Current practice is somewhere in between. For the most part, the use of bioassays is limited to a single test system, and the results are usually interpreted as either positive or negative. That is, binary information is the usual result of a bioassay evaluation. Our work over the past decade has facilitated the development of an alternative approach to interpreting bioassay results. The key element in our approach is the use of relative comparisons. Relative comparisons between responses of a given test system using wastewater and a well-known agent allow a graded response for each different bioassay. By using a battery of different bioassay systems, each with different mechanisms of toxicity, we are able to characterize the composite toxicological response to a wastewater sample with respect to a well-studied “reference” chemical. The value of this approach is that, if the use of the reference chemical has acceptable risk to the majority of the population or at least a known human risk, the wastewater can be evaluated with respect to that factor. We use water chlorination as a “reference” material in this report to illustrate the concept.

In vitro toxicity screening of dielectric gases using mammalian cells

The potential of various dielectric gases to cause cellular death was assayed in an in vitro cell culture system using Chinese hamster V79 (lung) cells. Exposures were carried out in small tubes which were constantly rotated, so that cells were exposed to the gas with only a thin layer of culture liquid interposed. Results indicated that SF/sub 6/ was essentially without cytotoxic effect, but after discharge of 16 kJ total spark energy in 60 cm/sup 3/ of SF/sub 6/, such samples of freshly sparked gas were quite cytotoxic (approx. 60% and 90% cell death following 1 and 4 hr exposures, respectively. The toxicity of these sparked samples was observed within 15 min of exposure of the cells (approx. 60% cell killing), and the degree of cell death increased with time of exposure, at least up to 2 hrs. The cytotoxicity of sparked SF/sub 6/ samples decreased with time of storage, so that after 4 wks, such samples were only minimally cytotoxic. Increasing spark energy produced samples with increased cytotoxic activity (1.6 kJ caused approx. 70% cell death after a 4 hr exposure, while 160 kJ of spark energy resulted in total cytotoxicity, after 1 hr).

ON THE APPLICATION OF SHORT TERM BIOTESTS TO HEALTH RISK ANALYSIS OF FLUORINATED COMPOUNDS

The use of various fluorinated compounds as insulating media for electric power transmission facilities is an example of a developing technology which may affect human health. Data on cytotoxicity, generated when the species, Saccharomyces cerevisiae, was exposed to perfluoro-2-butyne (PFB), sulfur hexafluoride (SF/sub 6/), sulfur dioxide (SO/sub 2/), octafluorocyclobutane (c-C/sub 4/F/sub 8/), and hexafluorocyclobutene (c-C/sub 4/F/sub 6/) are discussed. How such data when combined with biological data on well characterized toxic agents, can serve as input to an estimate of the human health impact or acceptable exposure limits for these fluorinated compounds is described.