Unintentional drinking-water contamination events of unknown origin: surrogate for terrorism preparedness.

Drinking-water is a direct conduit to many human receptors. An intentional attack (e.g. terrorism) on drinking-water systems can shock and disrupt elements of national infrastructures. We report on an unintentional drinking-water contamination event that occurred in Tel Aviv, Israel in July, 2001. Initially of unknown origin, this event involved risk management strategies used by the Ministry of Health for abating a potential public health crisis as might be envisaged of water contamination due to terrorism. In an abrupt event of unknown origin, public health officials need to be responsible for the same level of preparedness and risk communication. This is emphasized by comparison of management strategies between the Tel Aviv event and one of dire consequences that occurred in Camelford, England in 1988. From the onset of the Tel Aviv incident, the public health strategy was to employ the precautionary principle by warning residents of the affected region to not drink tap water, even if boiled. This strategy was in contrast to an earlier crisis that occurred in Camelford, England in 1988. An outcome of this event was heightened awareness that a water crisis can occur in peacetime and not only in association with terrorism. No matter how minor the contamination event or short-term the disruption of delivery of safe drinking-water, psychological, medical and public health impact could be significant.

Gestational exposure to high perchlorate concentrations in drinking water and neonatal thyroxine levels.

OBJECTIVE: To assess the effect of gestational perchlorate exposure through drinking water on neonatal thyroxine (T(4)). DESIGN: T(4) values were compared among newborns in Ramat Hasharon, Israel, whose mothers resided in suburbs where drinking water contained perchlorate < or = 340 microg/L (very high exposure, n = 97), 42-94 microg/L (high exposure, n = 216), and < 3 microg/L (low exposure, n = 843). In the very high and high exposure areas, T(4) values in newborns whose mothers drank tap water exclusively (as determined by a telephone interview) were analyzed as a subset. Serum perchlorate levels in blood from donors residing in the area were used as proxy indicators of exposure. MAIN OUTCOME: Neonatal T(4) values (mean +/- SD) in the very high, high, and low exposure groups were 13.9 +/- 3.8, 13.9 +/- 3.4, and 14.0 +/- 3.5 microg/dL, respectively (p = NS). Serum perchlorate concentrations in blood from donors residing in areas corresponding to these groups were 5.99 +/- 3.89, 1.19 +/- 1.37, and 0.44 +/- 0.55 microg/L, respectively. T(4) levels of neonates with putative gestational exposure to perchlorate in drinking water were not statistically different from controls. CONCLUSION: This study finds no change in neonatal T(4) levels despite maternal consumption of drinking water that contains perchlorate at levels in excess of the Environmental Protection Agency (EPA) drinking water equivalent level (24.5 microg/L) based on the National Research Council reference dose (RfD) [0.7 microg/(kg.day)]. Therefore the perchlorate RfD is likely to be protective of thyroid function in neonates of mothers with adequate iodide intake.

Antioxidant defenses in killifish (Fundulus heteroclitus) exposed to contaminated sediments and model prooxidants: short-term and heritable responses.

A population of killifish (Fundulus heteroclitus) inhabiting a Superfund site on the Elizabeth River (VA, USA) is tolerant of the acute toxicity of the sediments from the site; previous work suggests that this tolerance is based both on genetic adaptation and physiological acclimation. In this study, larval first- and second-generation (F1 and F2) offspring of Elizabeth River killifish were more resistant to the toxicity of t-butyl hydroperoxide (a model prooxidant) than were King's Creek (reference site) offspring, indicating a heritable tolerance of exposure to oxidative stress. In laboratory experiments designed to elucidate the mechanistic basis for this increased tolerance, we exposed laboratory-raised F1 and F2 offspring from Elizabeth River and King's Creek killifish to Elizabeth River sediments, menadione, or t-butyl hydroperoxide, and measured the following antioxidant parameters: total oxyradical scavenging capacity (TOSC); glutathione content (total and disulfide); activities of glutathione reductase (GR); glutathione peroxidase (GPx); and glutamate cysteine ligase (GCL) activities and protein levels of copper-zinc superoxide dismutase (CuZnSOD); and protein levels of manganese superoxide dismutase (MnSOD). Exposure to Elizabeth River sediments lead to consistent increases in total glutathione concentrations, GR activities, and MnSOD protein levels, and in some cases increased GPx and GCL activities, in both populations. In addition, Elizabeth River offspring (larvae) showed higher basal TOSC values, glutathione concentrations, and MnSOD protein levels. These data suggest that upregulated antioxidant defenses play a role in both short-term (physiological) and heritable (multigenerational/evolutionary) tolerance of the toxicity of these Superfund sediments. The responses of specific antioxidant parameters, including sex-specific responses in the cases of glutathione concentrations and GR activity, are also discussed.

A tap water turbidity crisis in Tel Aviv, Israel, due to technical failure: toxicological and risk management issues.

Herein, we report on the actual events linked to an ammonia spillage into the main waterline of the Tel-Aviv metropolitan area and its surrounding municipalities. Based upon a large magnitude increase of unknown origin in the turbidity and ammonia levels of the main drinking water supply, area residents were warned of possible serious contamination and advised to refrain from drinking tap water until further notice. Turbidity was later linked only to CaCO3, which was precipitated from the water due to the rise in pH caused by the excessive ammonia levels. The source of the ammonia (a malfunction of the measurement buoy in the ammonia tank) was not identified until several days after the warning was issued. The toxicological implications of the turbidity and ammonia elevations are considered and reconciled with the management strategies that followed. Of consequence to the management of this crisis was the approach of Ministry of Health officials to regard the ammonia, from the onset, as an indicator of several possible sources of origin rather than as a contaminant. Decision-making policies were hampered by ineffective communication between the national water supplier and government health officials. An outcome of this crisis was a heightened awareness of the potential of a water crisis occurring during peace time and not only in association with terrorist activities, to which Israeli citizens are highly sensitized. Finally, the present paper may serve to guide municipal environmental and health officials more appropriately in the event of similar drinking water crises in Israel or elsewhere.

Integrating enzymatic responses to organic chemical exposure with total oxyradical absorbing capacity and DNA damage in the European eel Anguilla anguilla.

In this work, susceptibility to oxidative stress was analyzed under laboratory conditions in the European eel Anguilla anguilla. Eels were treated with increasing concentrations of benchmark environmental pollutants, namely, benzo[a]pyrene ([BaP], at 0, 0.1, 1, 10, and 50 mg/kg), beta-naphthoflavone ([BNF], at 0, 0.1, 1, 10, and 50 mg/kg), Arochlor 1254 (at 0, 0.1, 1, 10, and 50 mg/kg), and 2,3,7,8-tetrachlorodibenzo p-dioxin ([TCDD], at 0, 0.01, 0.1, 1, and 2 microg/kg). The integral relationships were analyzed between induction of ethoxyresorufin O-deethylase (EROD) activity, its involvement in perturbing oxyradical metabolism, and the role of cytochrome P450 and/or oxidative stress in mediating genotoxic effects. To reveal whether the oxidative status in exposed organisms was altered as a result of chemical exposure, measurements of the main endogenous antioxidant defenses were integrated with the measurement of total oxyradical scavenging capacity (TOSC) toward peroxyl radicals and hydroxyl radicals (*OH). This approach permits discriminating the resistance of a tissue toward different forms of oxyradicals, thereby indicating a differential role for specific reactive oxygen species (ROS) in perturbing the balance between prooxidant and antioxidant mechanisms. All the analyzed chemicals promoted EROD induction (reflective of CYP1A) and altered either the levels or the activities of the antioxidants studied, which might be anticipated to exert alterations in oxyradical metabolism. Analysis of TOSC suggested the prevalence of metabolic oxidative pathways leading to the more reactive *OH on exposure to the chemicals studied. Of these chemicals, enhanced EROD activity correlated with genotoxic damage only in the cases of the nonhalogenated hydrocarbons BaP and BNF. The highest degree of genotoxic damage was consistently observed in organisms in which the capacity to absorb or scavenge OH was lowest. These data suggest a general relationship between oxidative stress and loss of DNA integrity in juvenile eels exposed to the chemicals studied herein.

Application of biomarkers for assessing the biological impact of dredged materials in the Mediterranean: the relationship between antioxidant responses and susceptibility to oxidative stress in the red mullet (Mullus barbatus).

In the period 1997-2000, approximately 1,800,000 m3 of material dredged from the Port of Leghorn was discharged into a sea dumping site located 14 miles from the coast. The red mullet (Mullus barbatus) was used as a bioindicator species for monitoring the biological impact of these discharges on a geographical and temporal scale. Organisms were sampled over three years (1998-2000) at different stations and several biomarkers, both of exposure and effect, were analyzed. Bioavailability of specific classes of pollutants was evaluated by analyzing levels of metallothioneins, the activity of cytochrome P450 1A (CYPIA) and of glutathione S-transferases. Among biomarkers of effect, special attention was paid to the balance between prooxidant challenge and antioxidant defenses, and to the appearance of damage caused by oxidative stress. The analyses of the main components of the antioxidant system included superoxide dismutase, catalase, glutathione peroxidases, glutathione reductase, glyoxalase I and II, and total glutathione. These data were integrated with the measurement of total oxyradical scavenging capacity (TOSC) as an indication of the overall biological resistance to toxicity of different forms of oxyradicals (peroxyl radicals, hydroxyl radicals and peroxynitrite). Results indicated a biological impact in organisms sampled near the disposal site; the impact was particularly evident during 1999 and mainly related to organic chemicals such as PAH. Exposure to these pollutants also caused variations in the levels and activity of several antioxidants. The analysis of TOSC, however, revealed that the overall capacity of specific tissues of organisms to absorb various oxidants was not seriously compromised when challenged with increased prooxidant pressures. Variations of single antioxidants were useful in revealing early warning "biological responses", while integration with TOSC analyses indicated if such changes also reflect a more integrated and functional "biological effect" with possible consequences at the organisms level. The red mullet appears to be a useful sentinel species for a biomarker approach to monitoring impact caused by dredged materials.

Antioxidants and total oxyradical scavenging capacity during grass shrimp, Palaemonetes pugio, embryogenesis.

During embryogenesis in grass shrimp the capacity to scavenge oxyradicals increased as measured by the Total Oxyradical Scavenging Capacity (TOSC) assay. The increase in TOSC during embryogenesis was associated with increasing concentrations of a number of antioxidants, including coenzyme Q (ubiquinone), alpha-tocopherol and reduced glutathione. Glutathione concentrations ranged from 0.004 to 0.005 nmol/embryo in early embryo stages and reached concentrations between 0.16 to 0.23 nmol/embryo in late embryo stages. Ascorbate remained essentially constant (0.16-0.20 nmol/embryo) throughout embryogenesis and may provide the preponderance of TOSC during early embryo development. Carotenoids were associated with yolk lipovitellin and these antioxidants decreased as yolk was absorbed during embryogenesis. Astaxanthin and beta-carotene were identified in embryos with astaxanthin always the principal carotenoid. In early embryo stages there are maternally derived antioxidants but as embryogenesis proceeds there is an assembly of a complex antioxidant system by newly formed cells and tissues.

Bioorganic mechanisms of the formation of free radicals catalyzed by glucose oxidase.

In this communication, we have described the activation of several xenobiotics by glucose oxidase from Aspergillus niger. The following compounds are readily reduced by d-glucose, in the presence of glucose oxidase: p-nitroso-N,N-dimethylaniline, methyl-1,4-benzoquinone, and 7,7,8,8-tetracyano-quinodimethane. In each case, the products of enzymatic reduction undergo a dismutation reaction with the parent compound and thus afford the formation of free radicals. In some cases, and at an appropriate pH value, the transformation of a parent compound into free radicals is almost quantitative. Under optimal conditions, free radicals are stable for several minutes in aqueous solutions under physiological conditions.