An analysis of the health benefits associated with the use of MTBE reformulated gasoline and oxygenated fuels in reducing atmospheric concentrations of selected volatile organic compounds.

To assess the health benefits gained from the use of cleaner burning gasoline, an analysis was conducted of changes in the atmospheric concentration of eight VOCs: acetaldehyde, benzene, 1,3-butadiene, ethylbenzene, formaldehyde, POM, toluene, and xylenes resulting from the use of reformulated gasoline and oxyfuel containing the additive MTBE. Modeled ambient air concentrations of VOCs were used to assess three seasonally-based scenarios: baseline gasoline compared to (a) summer MTBE:RFG, (b) winter MTBE:RFG, and (c) MTBE oxyfuel. The model predicts that the addition of MTBE to RFG or oxyfuel will decrease acetaldehyde, benzene, 1,3-butadiene and POM, but increase formaldehyde tailpipe emissions. The increased formaldehyde emissions, however, will be offset by the reduction of formaldehyde formation in the atmosphere from other VOCs. Using a range of plausible risk estimates, the analysis predicts a positive health benefit, i.e., a decline in cancer incidence associated with use of MTBE:RFG and MTBE oxyfuel. Using EPA cancer risk estimates, reduction in 1,3-butadiene exposure accounts for the greatest health benefit while reduction of benzene exposure accounts for the greatest health benefits based on alternative risk estimates. An analysis of microenvironment monitoring data indicates that most exposures to VOCs are significantly below levels of concern based on established margin-of-safety standards. The analysis does suggest, however, that health effects associated with short-term exposures to acetaldehyde and benzene may warrant further investigation.

Benchmark Dose Workshop: criteria for use of a benchmark dose to estimate a reference dose.

The purpose of the Benchmark Dose Workshop was to assess the feasibility and implications of replacing the no observed adverse effect level (NOAEL) with a benchmark dose (BMD) when deriving reference doses and concentrations (RfDs and RfCs). The workshop participants supported the use of the BMD method to remove many of the limitations inherent in using the NOAEL approach. Participants endorsed in general the use of a BMD for all quantal noncancer health effects and endorsed in particular the BMD for assessing developmental toxicity based on data presented at the workshop. The discussions of implementation recognized the need to demonstrate that changing from a NOAEL to a BMD gives the risk manager more certain information on which to base decisions. Most participants agreed that the current NOAEL-derived RfDs and RfCs are sufficiently protective and should only be changed as data become available for estimating a BMD. It was recognized that to achieve general acceptance of the BMD approach, it will have to be applied to a variety of endpoints.

Effect of phospholipase A2 on purified gastric vesicles.

The phospholipid and fatty acid composition and role of phospholipids in enzyme and transport function of gastric (H+ + K+)-ATPase vesicles was studied using phospholipase A2 (bee venom). The composition (%) was phosphatidyl-choline (PC) 33%; sphingomyelin (sph) 25%; phosphatidylethanolamine (PE) 22%; phosphatidylserine (PS) 11%; and phosphatidylinositol (PI) 8%. The fatty acid composition showed a high degree of unsaturation. In both fresh and lyophilized preparations, even with prolonged incubation, only 50% of phospholipids were hydrolyzed, but the amount of PE and PS disappearing was increased following lyophilization. There was a marked decrease in K+-ATPase activity (75%) but essentially no loss of the associated K+ p-nitrophenyl phosphatase was found. ATPase activity could be largely restored by various phospholipids (PE greater than PC greater than PS). There was also an increase in Mg2+-ATPase activity, partially reversed in fresh preparations by the addition of phospholipids (PE greater than PS greater than PC). Proton transport activity of the preparation was rapidly inhibited, initially due to a large increase in the HCl permeability of the preparation. Associated with these enzymatic and functional changes, the ATP-induced conformational changes, as indicated by circular dichroism spectra were inhibited.

Phosphatidate phosphohydrolase activity in porcine pulmonary surfactant.

The composition and enzymatic activity of porcine surfactant obtained by lung lavage was examined. The ratio of phospholipid to protein was found to be 13 mg per mg. Phosphatidate phosphohydrolase (PAPase) activity was present in lavage surfactant, lamellar bodies isolated from porcine lung tissue, and lamellar bodies isolated from human amniotic fluid. The optimal pH of PAPase in surfactant in lamellar bodies was 6.0. Cholinephosphotransferase activity was also present gradient centrifugation of amniotic fluid, the highest PAPase specific activity was found in the fraction that banded at the 0.65 M sucrose interface, similar to lamellar bodies obtained from porcine lung. From these results, we conclude that the enzyme PAPase remains closely associated with the surface active lipids during the process of storage and secretion of surfactant.

Characterization of phosphatidate phosphohydrolase activity associated with isolated lamellar bodies.

It has been demonstrated that lamellar bodies isolated from porcine lung have L-alpha-phosphatidate phosphohydrolase (EC 3.1.3.4) activity which cannot be accounted for by microsomal or mitochondrial contamination. Phosphatidate phosphohydrolase activity associated with the lamellar bodies is relatively insensitive to Mg2+ and more heat labile than the activity associated with whole lung microsomes. The enzyme was found to be the most active phosphohydrolase present in isolated lamellar bodies and is inhibited by 5 mM Be2+. Lamellar bodies isolated from human and rat lung tissue were also found to have this activity, and the functional role of the enzyme in lamellar bodies is proposed in relation to glycerophospholipid metabolism.

Studies in the biosynthesis of hepatic and biliary lecithins.

Male rats with biliary cannulae were injected with linoleate-1-(14)C, stearate-1-(14)C, palmitate-9-10-(3)H, phosphate-(32)P, l-methionine-methyl-(14)C, and choline-methyl-(3)H in various combinations and the incorporation of these isotopes into the phospholipids of liver, bile, and plasma was determined for 1-4 hr. The results summarized below favor the view (a) that exchange of saturated fatty acids plays a role in the formation of lecithins; (b) that the unsaturated fatty acids do not undergo significant exchange and determine the pathway of biosynthesis of lecithins; and (c) that there is either more than one pool of CDP-choline in liver or a pathway of biosynthesis of lecithin from choline not involving CDP-choline as an intermediate. Linoleoyl lecithin of liver attained higher specific activity with respect to phosphate-(32)P and choline-methyl-(3)H than did arachidonoyl lecithin. Lecithin in bile attained higher specific activities with respect to phosphate-(32)P, choline-methyl-(3)H, and linoleate-1-(14)C than the corresponding hepatic lecithins. Stearate-1-(14)C and palmitate-9-10-(3)H attained highest specific activities in the hepatic lecithin fraction rich in arachidonic acid. The specific activity of hepatic phosphatidyl ethanolamine was lower with respect to saturated fatty acids, but much higher with respect to (32)P than any lecithin. The ratio of specific activity of (3)H in methyl groups from choline to (14)C in methyl groups from methionine in hepatic sphingomyelin was lower than in hepatic linoleoyl lecithin.