Dennis M. Opresko

Nitroaromatic Munition Compounds: Environmental Effects and Screening Values

Available data on the occurrence, transport, transformation, and toxicity of eight nitroaromatic munition compounds and their degradation products, TNT, TNB, DNB, DNA, 2-ADNT, RDX, HMX, and tetryl were used to identify potential fate in the environment and to calculate screening benchmarks or safe environmental levels for aquatic and terrestrial organisms. Results of monitoring studies revealed that some of these compounds persist at sites where they were produced or processed. Most of the compounds are present in soil, sediment, and surface water or groundwater at military sites. Soil adsorption coefficients indicate that these chemicals are only moderately adsorbed to soil and may leach to groundwater. Most of these compounds are transformed by abiotic or biotic mechanisms in environmental media. Primary transformation mechanisms involve photolysis (TNT, RDX, HMX, tetryl), hydrolysis (tetryl), and microbial degradation (TNT, TNB, DNB, DNA, 2-ADNT, and HMX). Microbial degradation for both nitro and nitramine aromatic compounds involves rapid reduction of nitro groups to amino groups, but further metabolism is slow. With the exception of DNB, complete mineralization did not usually occur under the conditions of the studies. RDX was resistant to microbial degradation. Available ecotoxicological data on acute and chronic studies with freshwater fish and invertebrates were summarized, and water quality criteria or ecotoxicological screening benchmarks were developed. Depending on the available data, criteria/benchmarks were calculated according to USEPA Tier I or Tier II guidelines. The munitions chemicals are moderately to highly toxic to freshwater organisms, with chronic screening values < 1 mg/L. For some chemicals, these low values are caused by inherent toxicity; in other cases, they result from the conservative methods used in the absence of data. For nonionic organic munitions chemicals, sediment quality benchmarks were calculated (based on Kow values and the final chronic value) according to USEPA guidelines. Available data indicate that none of the compounds is expected to bioconcentrate. In the same manner in which reference doses for humans are based on studies with laboratory animals, reference doses or screening benchmarks for wildlife may also be calculated by extrapolation among mammalian species. Chronic NOAELs for the compounds of interest were determined from available laboratory studies. Endpoints selected for wildlife species were those that diminish population growth or survival. Equivalent NOAELs for wildlife were calculated by scaling the test data on the basis of differences in body weight. Data on food and water intake for seven selected wildlife species--short-tailed shrew, white-footed mouse, meadow vole, cottontail rabbit, mink, red fox, and whitetail deer--were used to calculate NOAELs for oral intake. In the case of TNB, a comparison of toxicity data from studies conducted with both the white-footed mouse and the laboratory rat indicates that the white-footed mouse may be more resistant to the toxic effects of chemicals than the laboratory rat and may further indicate the lesser sensitivity of wildlife species to chemical insult. Chronic NOAEL values for the test species based on the laboratory studies indicate that, by the oral route of exposure, TNB and RDX are not highly toxic to mammalian species. However, as seen with TNB, values are less conservative when chronic studies are available or when studies were conducted with wildlife species. Insufficient data were located to calculate NOAELs for avian species. In the absence of criteria or guidelines for terrestrial plants, invertebrates, and soil heterotrophic processes, LOECs were used as screening benchmarks for effect levels in the environment. In most cases, too few data were available to derive a screening benchmark or to have a high degree of confidence in the benchmarks that were derived. (ABSTRACT TRUNCATED)

Organophosphate Nerve Agents

Publisher Summary The chemical warfare (CW) nerve agents primarily addressed in this chapter include the anticholinesterase nerve agents tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, all of which are, or have been, part of the US domestic munitions inventories. These agents are potent anticholinesterase compounds deliberately formulated to induce debilitating effects or death during wartime hostilities, and have been used by military authorities of several nations to develop munitions. All of the nerve agents under consideration are anticholinesterase compounds and induce accumulation of the neurotransmitter acetylcholine (ACh) at neural synapses and neuromuscular junctions by phosphorylating acetylcholinesterase (AChE). Depending on the route of exposure and amount absorbed, the PNS and/or CNS can be affected and muscarinic and/or nicotinic receptors may be stimulated. Interaction with other esterases may also occur, and direct effects to the nervous system have been observed. Exposure to acutely toxic concentrations of nerve agents can result in excessive bronchial, salivary, ocular, and intestinal secretions, sweating, miosis, bronchospasm, intestinal hypermotility, bradycardia, muscle fasciculations, twitching, weakness, paralysis, loss of consciousness, convulsions, depression of the central respiratory drive, and death. More recent global events have focused attention on the potential threat of chemical terrorism, especially at transportation hubs. For example, the deliberate release of nerve agent sarin at lethal concentrations in the Japanese cities of Matsumoto (1994) and Tokyo (1995) by a Japanese domestic terrorist group has illustrated that such attacks can be a reality and require advance emergency preparedness planning.

Development and Application of Acute Exposure Guideline Levels (AEGLs) for Chemical Warfare Nerve and Sulfur Mustard Agents

Acute exposure guideline levels (AEGLs) have been developed for the chemical warfare agents GB, GA, GD, GF, VX, and sulfur mustard. These AEGLs were approved by the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances after Federal Register publication and comment, and judged as scientifically valid by the National Research Council Committee on Toxicology Subcommittee on AEGLs. AEGLs represent general public exposure limits for durations ranging from 10 min to 8 h, and for three levels of severity (AEGL-1, AEGL-2, AEGL-3). Mild effects are possible at concentrations greater than AEGL-1, while life-threatening effects are expected at concentrations greater than AEGL-3. AEGLs can be applied to various civilian and national defense purposes, including evacuation and shelter-in-place protocols, reentry levels, protective clothing specifications, and analytical monitoring requirements. This report documents development and derivation of AEGL values for six key chemical warfare agents, and makes recommendations for their application to various potential exposure scenarios. This submission was sponsored by a contractor of the U.S. government under contract DE-AC05-00OR22725. Accordingly, the U.S. government retains a nonexclusive, royalty-free license to publish or reproduce these documents, or to allow others to do so, for U.S. government purposes. These documents may be freely distributed and used for noncommercial, scientific and educational purposes.

Ecotoxicity of Nitroaromatics to Aquatic and Terrestrial Species at Army Superfund Sites

Nitroaromatic compounds, including 2,4,6-trinitrotoluene, RDX, HMX, tetryl, and associated degradation products, are released into the environment during the manufacturing, loading, packing, and assembling of munitions atU.S. Army Ammunition Plants. With the exception of 2A46DNT, nitroaromatic compounds are more toxic to freshwater fishes (LC 5 0 s ranging from 0.4-32 mg/L) than to freshwater invertebrates (EC 5 0 s ranging from 3-100 mg/L). Rainbow trout are the most sensitive test species with LC 5 0 values ranging from 0.43 to 6.4 mg/L for TNT, RDX, and HMX. These compounds produce negative effects on reproductive endpoints in terrestrial mammals at doses >1 mg/kg/day. Limited data indicate that nitroaromatics are not toxic to terrestrial plants (LOECs ranging from 25-100 μg/g in soil) and soil invertebrates (LOEC of 200 μg/g). Additional studies need to be undertaken to completely characterize the toxicity of these compounds; however, the criteria and screening benchmarks presented in this paper can be used to assess the risks to indigenous flora and fauna at Army Superfund sites.

Deriving Toxicity Values for Organophosphate Nerve Agents: A Position Paper in Support of the Procedures and Rationale for Deriving Oral RfDs for Chemical Warfare Nerve Agents

During the process of deriving oral Reference Dose (RfDs) values for chemical warfare agents, several issues arose regarding the identification of adverse effect levels and the application of uncertainty factors. For those agents that function as cholinesterase inhibitors (e.g., agents VX, GA, GB, and GD), these issues included the following: (1) Is the endpoint of blood cholinesterase inhibition an indicator of toxicity or a biomarker of exposure? (2) Can an experimental animal species be more sensitive than humans, thereby eliminating the need for an animal-to-human uncertainty factor? (3) Can the uncertainty factor that is used to extrapolate from a lowest-observed adverse-effect-level (LOAEL) to a no-observed-adverse-effect-level (NOAEL) be less than the default value of 10? (4) Can an oral RfD be derived from non-oral toxicity data? (5) Can an uncertainty factor of less than 10 be used to extrapolate from subchronic to chronic exposure (e.g., is the critical effect adequately described by the subchro...

Cholinesterase Inhibitors as Chemical Warfare Agents: Community Preparedness Guidelines

Publisher Summary Chemical warfare nerve agents are potent anticholinesterase compounds deliberately formulated to induce debilitating effects or death during wartime hostilities. Because of their steep dose response, these agents have been used by military authorities of several nations to develop munitions, and have been deployed by certain domestic terrorists. A key need for both community emergency preparedness and installation restoration is the availability of health-based exposure guidelines derived in a transparent manner by contemporary methods of data analysis. The chapter summarizes guidelines for acute vapor and chronic ingestion exposure to the nerve agents, GA (tabun), GB (satin), GD (soman), GF (cyclosarin), and VX. The toxicological analysis and logic incorporated into the estimation of reference dose (RfDe), and AEGL values for these nerve agents employ standard protocols to govern management of Superfund sites, and extremely hazardous substances unintentionally released during industrial accidents or chemical spills. In addition, both parameters are considered critical to maintaining compliance with international treaty obligations governing the stockpile and destruction of chemical weapons. The nerve agent RfDe and AEGL values, are now available for application to civilian and military defense purposes, such as shelter-in-place and evacuation protocols, recovery and remediation levels, analytical monitoring requirements, and protective clothing specifications. These guidelines are intended to preserve public health by not only characterizing potentially harmful exposure levels, but also identifying levels at which minimal or no toxic effects are expected. The toxicological analyses, protocol, and logic incorporated into nerve agent chronic RfDe and AEGL guideline development are documented, and their recent use by civilian and military authorities is summarized.Publisher Summary Chemical warfare nerve agents are potent anticholinesterase compounds deliberately formulated to induce debilitating effects or death during wartime hostilities. Because of their steep dose response, these agents have been used by military authorities of several nations to develop munitions, and have been deployed by certain domestic terrorists. A key need for both community emergency preparedness and installation restoration is the availability of health-based exposure guidelines derived in a transparent manner by contemporary methods of data analysis. The chapter summarizes guidelines for acute vapor and chronic ingestion exposure to the nerve agents, GA (tabun), GB (satin), GD (soman), GF (cyclosarin), and VX. The toxicological analysis and logic incorporated into the estimation of reference dose (RfDe), and AEGL values for these nerve agents employ standard protocols to govern management of Superfund sites, and extremely hazardous substances unintentionally released during industrial accidents or chemical spills. In addition, both parameters are considered critical to maintaining compliance with international treaty obligations governing the stockpile and destruction of chemical weapons. The nerve agent RfDe and AEGL values, are now available for application to civilian and military defense purposes, such as shelter-in-place and evacuation protocols, recovery and remediation levels, analytical monitoring requirements, and protective clothing specifications. These guidelines are intended to preserve public health by not only characterizing potentially harmful exposure levels, but also identifying levels at which minimal or no toxic effects are expected. The toxicological analyses, protocol, and logic incorporated into nerve agent chronic RfDe and AEGL guideline development are documented, and their recent use by civilian and military authorities is summarized.

Chemical Warfare Agents: Current Status of Oral Reference Doses

A 1998 paper published in Reviews in Environmental Contamination and Toxicology (Opresko et al. 1998) documented the development of oral reference doses (RfDs) for several groups of chemical warfare agents; i.e., sulfur mustard agents, nitrogen mustard agents, organophosphate nerve agents, the arsenical lewisite, and cyanogen chloride. The development of these reference doses was initiated by the U.S. Army Environmental Center (USAEC) to support its continuing task of remediating sites potentially contaminated by past releases of hazardous substances. This action was taken under general provisions of the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA). The USAEC, which functions as the program manager for the Army’s Installation Restoration Program (IRP), determined that responsible and efficient cleanup of both active installations and formerly used defense sites (FUDS) contaminated with chemical warfare agent residues required key toxicological parameters for performing IRP site health risk assessments.

Using morphometrics, in situ observations and genetic characters to distinguish among commercially valuable Hawaiian black coral species; a redescription of Antipathes grandis Verrill, 1928 (Antipatharia : Antipathidae)

The commercially valuable Hawaiian black coral Antipathes grandis Verrill, 1928 is redescribed based on reexamination of the holotype from the Bernice P. Bishop Museum and field collections of 34 specimens from depths of 27–127 m. The first scanning electron micrographs of A. grandis skeletal spines are provided, along with a series of in situ colour photographs and morphometric measurements of spines and polyps. Three colour morphotypes were collected in the field (red, pale red, and white), none of which could be differentiated based on morphological or genetic characters (two mitochondrial and two nuclear markers). In situ observations are used in conjunction with morphological and genetic characters to distinguish among the commercially valuable Hawaiian black coral species A. grandis and A. griggi Opresko, 2009. A. grandis is differentiated from A. griggi by its finer and more irregular branching, smaller and more closely-spaced polyps, and conical spines that are smaller and not characterised by bifurcations towards their apex. Morphologically, the species most closely resembling A. grandis is A. caribbeana Opresko, 1996 from the Caribbean. Among analysed congenerics, DNA sequences of A. grandis were likewise most similar to those of A. caribbeana for three of the four molecular markers used in this study. A combination of low genetic variability, incomplete taxonomic sampling, and unexpected similarity between A. caribbeana and the unbranched whip coral Stichopathes cf. occidentalis (Gray, 1860), hindered our ability to determine the sister relationship of A. grandis. However, in no phylogenetic reconstruction did A. grandis group sister to its sympatric congener A. griggi.

Chapter 9 – Organophosphate Nerve Agents

Chemical warfare nerve agents are potent anticholinesterase compounds deliberately formulated to induce debilitating effects or death during wartime hostilities. A key need for both community emergency preparedness, and restoration of military installations where agents have been processed and/or stored, is access to concise and timely information on agent characteristics and treatment, as well as health-based exposure guidelines derived in a clear manner by contemporary methods of data analysis. These parameters are summarized for the nerve agents GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), and VX, as well as for agent GE. Toxicological analysis and logic incorporated into estimation of vapor exposure and ingestion guidelines for these agents is also summarized. Recent experimental data characterizing low-level nerve agent vapor exposures for multiple agents and species have placed existing guidelines in context and further substantiates their protective nature.

A new species of antipatharian coral (Cnidaria: Anthozoa: Antipatharia: Schizopathidae) from the Pacific coast of Costa Rica

Abstract A new species of antipatharian coral (Anthozoa: Antipatharia) is described from the Pacific coast of Costa Rica. Lillipathes ritamariae, new species, forms large, multi-branched, flabellate colonies that reach a height of 60 cm or more. The genus Lillipathes is characterized by pinnules in four rows and arranged in bilateral alternating pairs. In L. ritamariae, the pinnules occur in only two rows in portions of the corallum; however, the characteristic Lillipathes pinnulation pattern is common enough to support assigning this species to this genus. The species can be distinguished from its cogeners by its very short pinnules (mostly 1–1.5 cm in length) and the development of many of the lateral pinnules into pinnulated branches. In contrast, in L. wingi, the pinnules are up to 5 cm long and only a few in the colony develop into branches. In L. quadribrachiata, the pinnules are up to about 3 cm long, and in Lillipathes lilliei, the pinnules are more than 10 cm in length, and only a small number develop into branches.