Mutation spectra in salmonella of chlorinated, chloraminated, or ozonated drinking water extracts: comparison to MX.

Drinking water samples were prepared in a pilot-scale treatment plant by chlorination (Cl2), chloramination (NH2Cl), ozonation (O3), or O3 followed by Cl2 or NH2Cl; and the nonvolatile acidic organics of the raw and treated waters were extracted by XAD/ethyl acetate and evaluated for mutagenicity in Salmonella (-S9). The extracts were 2-8 times more mutagenic in TA100 than in TA98, and the mutagenic potencies of the water extracts ranked similarly in both strains: Cl2 > O3 + Cl2 > NH2Cl > O3 + NH2Cl > O3 > raw. 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), which was estimated to account for approximately 20% of the mutagenic activity of the extracts, was shown to be the most potent compound tested thus far in a prophage-induction assay in Escherichia coli and a forward-mutation assay in Salmonella TM677. The mutations in approximately 2,000 revertants of TA98 and TA100 induced by MX and the water extracts were analyzed by colony probe hybridization and polymerase chain reaction/DNA sequence analysis. The water extracts and MX produced similar mutation spectra, which consisted in TA100 of predominantly of GC-->TA transversions in the second position of the CCC (or GGG) target of the hisG46 allele. This spectrum resembles that produced by large aromatic compounds and is distinct from that produced by alkylating agents and the semivolatile drinking water mutagen dichloroacetic acid. In TA98, MX and those water extracts resulting from the introduction of the chlorine atom produced 50-70% hotspot 2-base deletions and 30-50% complex frameshifts (frameshifts with an adjacent base substitution--mostly GC-->TA transversions as found in TA100). No other compound or mixture is known to induce such high frequencies of complex frameshifts. These results suggest that MX and "MX-like" compounds (possibly halogenated aromatics, such as halogenated polycyclic aromatic hydrocarbons) account for much of the mutagenic activity and specificity of the nonvolatile organics in drinking water and that these halogenated organics are especially capable of promoting misincorporation by the DNA replication complex. This study provides further evidence that the mutation spectrum of a complex mixture reflects the dominance of one or a few classes of chemical mutagens within the mixture.

Urine mutagenicity and biochemical effects of the drinking water mutagen, 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX), following repeated oral administration to mice and rats.

Mutagenicity analysis of urine from rats treated by oral gavage with MX at a dose of 64 mg/kg for 14 days revealed that only 0.3% of the administered compound was excreted in a genotoxically active form. At lower doses, mutagenicity was not detectable. No evidence of micronucleus induction in peripheral blood erythrocytes was observed in mice treated similarly. These findings indicate that MX is extensively detoxified in vivo and is unlikely to cause genetic damage in systemic tissues except at relatively high doses where detoxification pathways become saturated. In a separate experiment, significant depressions were observed in D-glucaric acid and thioether excretion and in levels of several liver enzymes involved in xenobiotic metabolism. The mechanism for these metabolic alterations and their relevance to the in vivo metabolism of the compound require further investigation.

Glycerol hyperhydration in resting horses.

SUMMARY: To determine whether administration of glycerol-containing solutions induces a state of transient hyperhydration in resting euhydrated horses, changes in plasma and urine constituents were measured in four horses for 1 h before and 5 h after nasogastric administration of each of four treatments (Experiment 1). Treatments were applied in a randomized fashion and included: (1) 1.0 g.kg(-)(1)glycerol in 8 L of water (G); (2) 8 L of water (W); (3) 8 L of 0.9% NaCl solution (S); and (4) 1.0 g.kg(-)(1)glycerol in 8 L of 0.9% NaCl solution (GS). In a subsequent study, voluntary water intake was measured hourly for 5 h after nasogastric administration of each treatment (Experiment 2). All treatments produced mild plasma volume expansion ranging from 3.2 to 5.8% in Experiment 1. Administration of glycerol containing solutions increased serum glycerol concentration approximately 100-fold and plasma osmolality (P(osm)) by approximately 10 mOsm/kg and resulted in a tendency towards increased renal water conservation despite increased osmole excretion. In contrast, W treatment decreased plasma and urine osmolality and was accompanied by increased urine production and decreased renal water conservation. Plasma and urine osmolality, as well as renal osmole and water excretion, were unchanged after S administration. In Experiment 2, horses treated with GS voluntarily drank an additional 5.2 +/- 0.9 L of water during the initial hour following nasogastric administration of 8 L of solution. Voluntary water intake with the other treatments was less than 1.0 L for the entire 5 h observation period. Collectively, the results of both experiments suggest that administration of glycerol in saline would produce transient hyperhydration in resting euhydrated horses by enhancing renal water conservation and stimulating voluntary water intake.

Assessment of death attitudes: an empirical approach.

The Threat Index and the Death Anxiety Scale were administered to 228 subjects. Based on the high/low criterion scores, 105 subjects were assigned to the following four groups: (a) high death threat/high death anxiety, (b) high death threat/low death anxiety, (c) low death threat/high death anxiety, and (d) low death threat/low death anxiety. During the experimental phase of the study, subjects viewed a filmstrip on death rituals in various cultures. A recall test was then administered. Results indicated no significant group differences on recall performance. Initial no-show rates for the second part of the experiment were observed in the four groups reflecting a significant negative relationship between death anxiety and initial no-show rates. The possibility of defensive responding on the Death Anxiety Scale was suggested.