Saline groundwater in the Buffels River catchment, Namaqualand, South Africa: A new look at an old problem.

Namaqualand, South Africa, is a global biodiversity hotspot but local populations are affected by challenging economic conditions largely because of poor access to water. In this study groundwater types are characterised and sources of salts and salinisation processes are identified using hydrochemistry and δ18O, δ2H and 87Sr/86Sr data. Analysis of δ18O and δ2H data suggests that evaporation does not play a major role in salinisation of the groundwater. However, major ion chemistry and 87Sr/86Sr ratios indicate that salts present in the groundwater are linked to dry deposition of marine aerosols and ion-exchange reactions in soils in the alluvial aquifer systems. The hydrochemical variability of the groundwater in the basement aquifer system suggests that there are strong local controls linked to weathering processes in individual basement rock types. The region is also notable for the high density of heuweltjies, biophysical features associated with increased nutrient levels, associated with termite activity. Electromagnetic scanning as well as measurement of water-soluble soil electrical conductivity values on and off heuweltjies, show that heuweltjies are saline with salinity increasing with depth. The level of groundwater salinity correlates with the level of heuweltjie salinity. Precipitation records from the last 150 years provide support for the hypothesis that accumulated salts, and in particular, heuweltjie salts are flushed into the groundwater system during sporadic large volume precipitation events. Thus, heuweltjies and hence termite activity, could potentially represent a previously unrecognized contributor to groundwater salinisation across Namaqualand and in other parts of the world.

Primary lymphoma of the breast.

Primary lymphoma of the breast is a rare finding. Two cases and a review of the literature are presented.

The sources, fate, and toxicity of chemical warfare agent degradation products.

We include in this review an assessment of the formation, environmental fate, and mammalian and ecotoxicity of CW agent degradation products relevant to environmental and occupational health. These parent CW agents include several vesicants: sulfur mustards [undistilled sulfur mustard (H), sulfur mustard (HD), and an HD/agent T mixture (HT)]; nitrogen mustards [ethylbis(2-chloroethyl)amine (HN1), methylbis(2-chloroethyl)amine (HN2), tris(2-chloroethyl)amine (HN3)], and Lewisite; four nerve agents (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), tabun (GA), sarin (GB), and soman (GD)); and the blood agent cyanogen chloride. The degradation processes considered here include hydrolysis, microbial degradation, oxidation, and photolysis. We also briefly address decontamination but not combustion processes. Because CW agents are generally not considered very persistent, certain degradation products of significant persistence, even those that are not particularly toxic, may indicate previous CW agent presence or that degradation has occurred. Of those products for which there are data on both environmental fate and toxicity, only a few are both environmentally persistent and highly toxic. Major degradation products estimated to be of significant persistence (weeks to years) include thiodiglycol for HD; Lewisite oxide for Lewisite; and ethyl methyl phosphonic acid, methyl phosphonic acid, and possibly S-(2-diisopropylaminoethyl) methylphosphonothioic acid (EA 2192) for VX. Methyl phosphonic acid is also the ultimate hydrolysis product of both GB and GD. The GB product, isopropyl methylphosphonic acid, and a closely related contaminant of GB, diisopropyl methylphosphonate, are also persistent. Of all of these compounds, only Lewisite oxide and EA 2192 possess high mammalian toxicity. Unlike other CW agents, sulfur mustard agents (e.g., HD) are somewhat persistent; therefore, sites or conditions involving potential HD contamination should include an evaluation of both the agent and thiodiglycol.

Traumatic rupture of the thyroid gland.

A 24-year-old male presented with marked neck swelling following direct neck trauma. Imaging diagnosed a rare case of traumatic thyroid rupture.

Heterogeneous location of the mupA high-level mupirocin resistance gene in Staphylococcus aureus.

Epidemiologically unrelated clinical isolates of Staphylococcus aureus with high-level resistance to mupirocin (MIC > or = 512 mg/L) were studied to determine the location of the mupA resistance gene. The gene was carried on plasmids of variable size, some of which were transferable in vitro. DNA hybridisation of genomic DNA from 85 isolates showed that mupA was located on EcoRI fragments of seven different sizes; the most frequently observed fragments were 7 kb (46 isolates) or 4.1 kb (21 isolates). All isolates retained a 1.6-kb Nco I fragment that hybridised with mupA probes, but showed heterogeneous hybridisation patterns after digestion with Hinc II. These data suggested that mupA may be conserved, but that variation occurs in the flanking DNA proximal to it. Amplification of spacer regions between mupA and closest proximal copy of IS257 yielded products of variable size and was consistent with the presence of IS257 in either orientation. It is proposed that IS257-mediated events are responsible for the heterogeneity observed. The location of mupA varied between epidemiologically unrelated isolates of the same strain, including isolates of EMRSA-16 -- one of the two predominant methicillin-resistant strains in UK hospitals at the present time -- and this correlated with variations in the digestion patterns of the mupirocin resistance plasmids. The variable location of mupA should be evaluated further as a potential epidemiological tool with which to monitor the spread of high-level mupirocin resistance in EMRSA-16 or other strains of S. aureus.

Chemical warfare agents: estimating oral reference doses.

Health risk assessments for sites contaminated with chemical warfare agents require a comparison of the potential levels of exposure with a characterization of the toxic potency of each chemical. For noncancer health effects, toxic potency is expressed in terms of Reference Doses (RfD). A RfD is a daily exposure level or dose (usually expressed in units of milligrams of chemical per kilogram body weight per day) for the human population, including sensitive subpopulations, that is likely to be without an appreciable risk of deleterious effects. A daily exposure at or below the RfD is not likely to be associated with health risks, but as the amount of chemical that an individual is exposed to increases above the RfD, the probability that an adverse effect will occur also increases. A RfD is derived by first examining the available human or animal toxicity data to identify a dose or exposure that corresponds to a no-observed-adverse-effect level (NOAEL) or a lowest-observed-adverse-effect level (LOAEL). The NOAEL is the exposure level at which there are no statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. Effects may be produced at this level, but they are not considered to be adverse if they do not result in functional impairment or pathological lesions that affect the performance of the whole organism or which reduce an organism's ability to cope with additional challenge. The LOAEL is the lowest exposure level at which there are statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. If only a LOAEL is identified by the toxicity data, a NOAEL is estimated by dividing the LOAEL by a factor no greater than 10. This extrapolation factor of 10 or less is termed the LOAEL-to-NOAEL Uncertainty Factor (UFL). The NOAEL is also adjusted by the application of other Uncertainty Factors, including (1) a UFH < or = 10 to ensure that the resulting RfD protects segments of the human population that may be more sensitive to the chemical than the average person; (2) a UFA < or = 10 to extrapolate from the experimental animal species to humans; (3) a UFS < or = 10 to extrapolate from an experimental subchronic exposure study to a potential chronic exposure; and (4) a UFD < or = 10 to ensure that the resulting RfD is protective for all possible adverse effects, particularly those that may not have been adequately evaluated in the available studies. A Modifying Factor (MF), based on a qualitative professional assessment of the data, may also be used to account for other factors (e.g., deficiencies in the critical study) that are not adequately covered by the standard Uncertainty Factors. 1. Agent HD (Sulfur Mustard). RfDe = 7 x 10(-6) mg kg-1 d-1. A LOAEL was identified in a two-generation reproductive toxicity study conducted in rats. A total uncertainty factor of 3000 was applied to account for protection of sensitive subpopulations (10), animal-to-human extrapolation (10), LOAEL-to-NOAEL extrapolation (3), and extrapolation from a subchronic to chronic exposure (10). A LOAEL-to-NOAEL UF of 3, instead of the default value of 10, was used because the critical effect (stomach lesions) was considered to be "mild" in severity and may have been enhanced by the vehicle used (sesame oil in which sulfur mustard is fully soluble) and the route of administration (gavage), which is more likely to result in localized irritant effects. The key study did identify a toxic effect that is consistent with the vesicant properties of sulfur mustard. In none of the other available studies was there any indication of a different effect occurring at a lower exposure level.

Neurological problems presenting to an ophthalmic casualty department.

All patients presenting with neurological problems to an eye hospital casualty department over one year were prospectively studied. A total of 119 patients were identified. The most frequent diagnoses were retrobulbar neuritis (34; 28.5%), sixth cranial nerve palsy (22; 18.5%), third cranial nerve palsy (15; 12.6%) and Adie's tonic pupil (11; 9%). Cranial nerve palsies were most commonly due to diabetes or hypertension (16; 43.2%). Only one intracranial aneurysm was found. Symptoms included blurred vision (52; 43.7%), binocular diplopia (51; 42.8%), and eye pain (27; 22.7%). Fifty patients (42.0%) were referred by a general medical practitioner. Twenty-two (18.5%) were admitted to hospital. Forty-nine skull X-rays were requested and all were normal. Twenty-nine chest X-rays were requested. One (3.4%) showed an abnormality (carcinoma of the bronchus). Neurological patients present to ophthalmic casualty departments because of ophthalmic symptoms. Ophthalmic casualty officers are able to make working diagnoses and to direct patients appropriately. The use of investigations in the casualty department, however, is unlikely to be productive.

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects.

Characterizing biological variability in livestock blood cholinesterase activity for biomonitoring organophosphate nerve agent exposure.

A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock as a monitor of potential organophosphate nerve agent exposure during the planned destruction of US unitary chemical warfare agent stockpiles, is described. The experimental design included analysis of blood ChE activity in individual healthy sheep, horses, and dairy and beef cattle during a 10- to 12-month period. Castrated and sexually intact males, pregnant and lactating females, and adult and immature animals were examined through at least one reproductive cycle. The same animals were used throughout the period of observation and were not exposed to ChE-inhibiting organophosphate or carbamate compounds. A framework for an effective biomonitoring protocol within a monitoring area includes establishing individual baseline blood ChE activity for a sentinel group of 6 animals on the bases of blood samples collected over a 6-month period, monthly collection of blood samples for ChE-activity determination during monitoring, and selection of adult animals as sentinels. Exposure to ChE-inhibiting compounds would be suspected when all blood ChE activity of all animals within the sentinel group are decreased greater than 20% from their own baseline value. Sentinel species selection is primarily a logistical and operational concern; however, sheep appear to be the species of choice because within-individual baseline ChE activity and among age and gender group ChE activity in sheep had the least variability, compared with data from other species. This protocol provides an effective and efficient means for detecting abnormal depressions in blood ChE activity in livestock and can serve as a valuable indicator of the extent of actual plume movement and/or deposition in the event of organophosphate nerve agent release.

Relative potency estimates of acceptable residues and reentry intervals after nerve agent release.

In the event of an unplanned release of a chemical warfare agent during any stage of the Chemical Stockpile Disposal Program, the potential exists for off-post contamination of drinking water, forage crops, grains, garden produce, and livestock. The more persistent agents, such as the organophosphate nerve agent VX, pose the greatest human health concern for reentry. A relative potency approach comparing the toxicity of VX to organophosphate insecticide analogues is developed and used to estimate allowable residues for VX in agricultural products and reentry intervals for public access to contaminated areas. Analysis of mammalian LD50 data by all exposure routes indicates that VX is 10(3) to 10(4) times more toxic than most commercially available organophosphate insecticides. Thus, allowable residues of VX could be considered at concentration levels 10(3) to 10(4) lower than those established for certain insecticides by the U.S. EPA. Evaluation of reentry intervals developed for these organophosphate analogues indicate that, if environmental monitoring cannot reliably demonstrate acceptable levels of VX, restricted access to suspect or contaminated areas may be on the order of weeks to months following agent release. Planning for relocation, mass care centers, and quarantine should take this time period into account.

Treating exposure to chemical warfare agents: implications for health care providers and community emergency planning.

Current treatment protocols for exposure to nerve and vesicant agents found in the U.S. stockpile of unitary chemical weapons are summarized, and the toxicities of available antidotes are evaluated. The status of the most promising of the new nerve agent antidotes is reviewed. In the U.S. atropine and pralidoxime compose the only approved antidote regimen for organophosphate nerve agent poisoning. Diazepam may also be used if necessary to control convulsions. To avoid death, administration must occur within minutes of substantial exposure together with immediate decontamination. Continuous observation and repeated administration of antidotes are necessary as symptoms warrant. Available antidotes do not necessarily prevent respiratory failure or incapacitation. The toxicity of the antidotes themselves and the individualized nature of medical care preclude recommending that autoinjectors be distributed to the general public. In addition, precautionary administration of protective drugs to the general population would not be feasible or desirable. No antidote exists for poisoning by the vesicant sulfur mustard (H, HD, HT); effective intervention can only be accomplished by rapid decontamination followed by palliative treatment of symptoms. British anti-Lewisite (BAL) (2,3-dimercapto-1-propanolol) is the antidote of choice for treatment of exposure to Lewisite, another potent vesicant. Experimental water-soluble BAL analogues have been developed that are less toxic than BAL. Treatment protocols for each antidote are summarized in tabular form for use by health care providers.

Oral fluorescein angiography: reassessment of its relative safety and evaluation of optimum conditions with use of capsules.

Injection of fluorescein intravenously for fundal angiography is associated with a high incidence of minor adverse effects (21%) but a very low incidence of serious (life threatening) reactions (0.05%). A serious reaction may occur without warning in a patient with no history of atopy. There are no reports of oral fluorescein causing a serious reaction, and minor adverse effects are uncommon. A study was undertaken to determine optimum conditions for oral fluorescein angiography. Capsules proved more convenient than a solution for ingestion of fluorescein. A dose of 25 mg/kg body weight produced good quality angiograms in 75% of the patients. The best pictures were obtained by photographing the fundus after 40 and 60 minutes.

Chlorination, water hardness and serum cholesterol in forty-six Wisconsin communities.

The Wisconsin Heart Health Research Program measured serum lipids and other clinical parameters among residents of 46 neighbouring small communities in central Wisconsin. The purpose of the study was to determine whether distribution of serum lipids, blood pressure or thyroid hormones differed according to the chlorination of water supply, or to its calcium and magnesium content (hardness). This report examines serum lipid levels in relation to the drinking water characteristics chlorination and hardness. Variables measured on individuals included age, education level, alcohol intake, cigarette smoking, dietary fat and dietary calcium. An analysis of covariance was used to estimate effects of chlorination and hardness on each of the serum lipids, with individual variables included as covariates. Among females, serum cholesterol (SC) levels are significantly higher in chlorinated communities than in non-chlorinated communities. Community SC levels are also higher for males in chlorinated communities, on the average, but differences are smaller and not statistically significant. Low density lipoprotein (LDL) cholesterol levels follow a similar pattern to that for total SC levels, higher in chlorinated communities for females, but not different for males. On the other hand, high density lipoprotein (HDL) cholesterol community means are nearly identical in the chlorinated and non-chlorinated communities for each sex.

Arylamine N-acetyltransferase from fast (C57BL6) and slow (A/J) N-acetylating strains of mice.

Many drugs and xenobiotics which are arylamines or hydrazines are metabolized by N-acetyltransferase. The enzyme is polymorphically expressed in humans and inbred strains of laboratory animals can be classified as fast or slow acetylating strains. N-Acetyltransferase has been partially purified from livers from a fast acetylator, C57BL6, and a slow acetylator, A/J, strain of mouse. The enzyme has been purified 1900- and 955-fold, respectively from the two strains, but still represents less than 20% of the total protein. These studies show that at least 5000-fold purification is required to isolate mouse liver N-acetyltransferase from either strain. During purification, N-acetyltransferase from both strains of mice elute identically as a single peak on ion exchange chromatography. Sucrose density gradient centrifugation of N-acetyltransferase shows partial separation of the activity from A/J mice into two peaks whilst the enzyme from C57BL6 mice migrates as one peak which is distinct from both the major and minor types of N-acetyltransferase in A/J mouse liver. The hydrodynamic parameters of N-acetyltransferase from C57BL6 mice and the major peak of N-acetyltransferase from A/J mice show that these enzymes are likely to be monomers of apparent molecular weights 33,000 +/- 1000 and 30,000 +/- 2000, respectively. These results indicate that the N-acetyltransferase isozymes in liver of these two strains of mice are not identical.

Disposing of the US chemical weapons stockpile. An approaching reality.

A congressional mandate to dispose of the current US stockpile of lethal unitary weapons (Public Law 99-145, Department of Defense Authorization Act of 1986) has international implications and is responsible for a recent major assessment of available disposal alternatives. Eight installations in the continental United States currently host aging stockpiles of chemical warfare agents. The stockpiles are described, the toxicology and physical properties of each agent are characterized, disposal options considered by the US Army are identified, and the role of a programmatic health and environmental assessment in the decision-making process is outlined. Critical findings are that existing community emergency planning and preparedness are inadequate and that communication of risk information requires significant improvement. Measures are under way to address these needs. However, timely disposal of the stockpile entails less of a hazard than continued storage.

Sulfur mustard as a carcinogen: application of relative potency analysis to the chemical warfare agents H, HD, and HT.

A relative potency method for assessing potential human health effects from exposures to relatively untested chemicals is presented and documented. The need for such a method in evaluating the carcinogenic potential of the chemical warfare agent sulfur mustard (agent HD) from a limited data base is specifically addressed. The best-estimate potency factor for sulfur mustard relative to benzo[a]pyrene is 1.3, with an interquartile range of 0.6 to 2.9. The method is applied to (1) the estimated fence-boundary air concentrations of mustard during operation of a proposed agent incinerator at Aberdeen Proving Ground (APG), Maryland, and (2) the current approved general population exposure level of 1 X 10(-4) mg HD/m3 and the occupational exposure level of 3 X 10(-3) mg HD/m3. Maximum estimates of excess lifetime cancer risk for individuals at sites along the APG boundary range between 3 X 10(-8) and 1 X 10(-7). Lifetime cancer risk estimates less than or equal to 10(-6) are not now regulated by the U.S. Environmental Protection Agency or the Food and Drug Administration. Maximum estimates of excess lifetime cancer risk assuming daily exposure to the approved standards during the proposed 5 years of incinerator operation are on the order of 10(-5) for the general public and 10(-4) for the worker population. These values are considered upper limit estimates.

Plasma concentrations of catecholamines following intraocular irrigation with adrenaline.

Plasma concentrations of adrenaline and noradrenaline were measured in 13 patients undergoing cataract surgery after intraocular irrigation with an adrenaline-containing solution. Venous blood samples were withdrawn before, during and after intraocular irrigation with a solution of adrenaline 1:500,000. Plasma concentrations of both adrenaline and noradrenaline did not differ significantly from those noted before induction of anaesthesia.