Anticonvulsant treatment of nerve agent seizures: anticholinergics versus diazepam in soman-intoxicated guinea pigs.

A total of eight anticholinergic drugs (aprophen, atropine, azaprophen, benactyzine, biperiden, procyclidine, scopolamine, trihexyphenidyl) were tested in parallel with diazepam for the ability to terminate seizure activity induced by the nerve agent soman. Guinea pigs, implanted with electrodes to record cortical electroencephalographic (EEG) activity, were pretreated with pyridostigmine Br (0.026 mg/kg, i.m.) and 30 min later challenged with 2 x LD50 soman (56 microg/kg, s.c.) followed 1 min later by treatment with atropine SO4 (2 mg/kg, i.m.) and pralidoxime chloride (2-PAM Cl; 25 mg/kg, i.m.). All guinea pigs developed sustained seizure activity following this treatment. Dose-effect curves were determined for the ability of each drug to terminate seizure activity when anticonvulsant treatment was given either 5 or 40 min after seizure onset. Body weight gain and recovery of behavioral performance of a previously trained one-way avoidance task were measured after exposure. With the exception of atropine, all anticholinergic drugs were effective at lower doses than diazepam in terminating seizures when given 5 min after seizure onset; benactyzine, procyclidine and aprophen terminated seizures most rapidly while scopolamine, trihexyphenidyl, biperiden, and diazepam were significantly slower. When given 40 min after seizure onset, diazepam was the most potent compound tested, followed by scopolamine, benactyzine and biperiden; atropine was not effective when tested 40 min after seizure onset. For diazepam, the time to terminate the seizure was the same whether it was given at the 5- or 40-min delay. In contrast, most anticholinergics were significantly slower in terminating seizure activity when

Use of probabilistic methods to understand the conservatism in California's approach to assessing health risks posed by air contaminants.

Many state and federal agencies have prepared risk assessment guidelines, which describe methods for quantifying health risks associated with exposure to vapors and particulates emitted from point and area sources (e.g., California Air Pollution Control Officers Association [CAPCOA] under the Air Toxics "Hot Spots" Act [Assembly Bill 2588] and the U.S. Environmental Protection Agency [EPA] under the Clean Air Act). In general, these guidelines recommend or require the use of upperbound "point" estimates for numerous exposure parameters. This methodology yields a single risk estimate, which is intended not to underestimate the true risk and may significantly overstate it. This paper describes a risk assessment of a facility's airborne emissions using a probabilistic approach, which presents a range and distribution of risk estimates rather than a single point estimate. The health risks to residents living near a food processing facility, as estimated using techniques recommended by California AB2588, are compared to the results of a probabilistic analysis. Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were identified as the emitted chemicals of concern. The point estimate method recommended by CAPCOA resulted in estimates that were greater than the 99.99th percentile risk predicted by the probabilistic analysis. As shown in other assessments of persistent airborne chemicals, secondary or indirect exposure pathways (i.e., ingestion of beef, ingestion of cow's milk, and ingestion of mother's milk) rather than inhalation, were the greatest contributors to risk. In this analysis, the probability distributions for the cancer potency factor and ingestion of cow's milk had the largest impact on the results of the 33 exposure factors considered.

Comparing the results of a Monte Carlo analysis with EPA's reasonable maximum exposed individual (RMEI): a case study of a former wood treatment site.

In the United States, there are about 250 former sites that treated wood with preservatives that are now in need of some degree of remediation. The soil at many of these sites is contaminated with creosote, polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). This paper compares the results of the current USEPA point estimate (deterministic) approach for predicting the health risks associated with exposure to PCDDs/PCDFs in soil with the results of a probabilistic approach which uses a Monte Carlo analysis. At many of these wood treatment sites the hazard posed by the PAHs, and especially pentachlorophenol, can be much greater than that due to PCDD and PCDFs; however, because at this site the health risk associated with PAHs was deemed negligible by ATSDR, only PCDDs/PCDFs were evaluated. Octachlorodibenzo-p-dioxin (OCDD) and octachlorodibenzofuran (OCDF) congeners were evaluated independently from the other congeners due to their prevalence in the environment and the availability of congener-specific data. The results of the reevaluation of the rodent bioassay data for 2,3,7,8-TCDD were considered in the probability distribution for the cancer potency factor. The authors' analyses indicate that when assessing exposure to soil via inhalation, ingestion, and dermal contact, the current regulatory approach used to estimate the reasonable maximally exposed individual (RMEI) (USEPA, Risk Assessment Guidance for Superfund, Vol. 1, Part A, 1989) can predict risks which are 10- to 100-fold greater than the 95th percentile risk predicted by a Monte Carlo analysis.

Prevention in Virginia: Ten years of progress.

Speaking to the participants of Virginia's First Prevention Institute in 1988, Stephen Goldston, previous Director of NIMH'S Prevention Division asked, "Why is it that as I go from state to state learning about their prevention programs I hear that fewer and fewer dollars are going into prevention, but in Virginia prevention seems to be growing at a steady pace"? Goldston's perception of Virginia is quite accurate. Moreover, 1988 will probably be seen as a major benchmark in the growth of prevention services in the Commonwealth because the Virginia Department of Mental Health, Mental Retardation and Substance Abuse Services (VA DMHMRSAS) established specific priorities for prevention services and a separate funding stream so that these priorities could be offered by the localities. These actions represent major strides for Virginia's prevention community, strides that began with the Legislature in 1980.