No abstract

Ashes, obtained from about one-fourth of the operating municipal refuse incinerators in the United States, were analyzed for a range of organic toxicants and mutagens. Thirty percent of the ash samples, which consisted of bottom ash or bottom ash-fly ash mixtures, contained 20-74% organic matter. Thirty percent of the ashes contained direct-acting and/or promutagens which revertedSalmonella typhimurium TA98 or TA100. Sixty percent of the ashes contained more than 5 ng/g of polychlorinated biphenyls. The concentration of tetra- and pentachlorinated biphenyls were higher than the mono-, di-, hepta- and octachlorinated biphenyls. A similar distribution of congeners was seen in polychlorinated dibenzodioxins found in the ashes. The major volatileN-nitroso compounds found in the ashes wereN-nitrosodimethylamine andN-nitrosomorpholine. Other classes of compounds which were found in the ashes included chlorinated benzenes, phthalates, and substituted benzothiophenes.

bWith increasing resistance to existing antimalarials, there is an urgent need to discover new drugs at affordable prices for countries in which malaria is endemic. One approach to the development of new antimalarial drugs is to improve upon existing antimalarial agents, such as the tetracyclines. Tetracyclines exhibit potent, albeit relatively slow, action against malaria parasites, and doxycycline is used for both treatment (with other agents) and prevention of malaria. We synthesized 18 novel 7-position modified tetracycline derivatives and screened them for activity against cultured malaria parasites. Compounds with potent in vitro activity and other favorable drug properties were further tested in a rodent malaria model. Ten compounds inhibited the development of cultured Plasmodium falciparum with a 50% inhibitory concentration (IC 50 ) after 96 h of incubation of <30 nM, demonstrating activity markedly superior to that of doxycycline (IC 50 at 96 h of 320 nM). Most compounds showed little mammalian cell cytotoxicity and no evidence of in vitro phototoxicity. In a murine Plasmodium berghei model, 13 compounds demonstrated improved activity relative to that of doxycycline. In summary, 7-position modified tetracyclines offer improved activity against malaria parasites compared to doxycycline. Optimized compounds may allow lower doses for treatment and chemoprophylaxis. If safety margins are adequate, dosing in children, the group at greatest risk for malaria in countries in which it is endemic, may be feasible.

Traditional Korean soysauce samples were collected from households in Chinju, Gyeongnam, Korea and analysed for volatile N-nitrosamines. Five of 24 samples contained NDMA (range = 1.6-10.4 micrograms/l) which was the only volatile N-nitroso compound found. Soysauce made from well water contained NDMA more often (4 of 6 samples) than soysauce made from tap water (1 of 18). This suggests that the water source is a determinate in the NDMA content of soysauce, probably due to a higher nitrate content of well water. The source of salt used did not clearly influence NDMA content. Soysauce was prepared in the laboratory using traditional methods but with 0 to 400 mg/l nitrate and in some cases made 6.5 to 65 mM in ascorbic acid and fermented for 120 days. The NDMA content of the samples was positively correlated with increasing nitrate concentration. Nitrate at 400 mg/l resulted in an NDMA content of 203 micrograms/l. Ascorbic acid substantially inhibited NDMA formation. All samples contained large numbers of nitrate reductase-containing organisms (greater than 1 x 10(7) CFU/ml).