1、Designation: E 2552 08Standard Guide forAssessing the Environmental and Human Health Impacts ofNew Energetic Compounds1This standard is issued under the fixed designation E 2552; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision, the
2、year of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon (e) indicates an editorial change since the last revision or reapproval.INTRODUCTIONSustaining training operations while maintaining force health is vital to national security. Researchefforts
3、are underway to identify energetic substances that have negligible environmental impacts andimplement them in military munitions. This guide is intended to provide a standardized method toevaluate the potential environmental impacts of prospective candidate energetic substances. This guideis intende
4、d for use by technical persons with a broad knowledge of risk assessment, fate and transportprocesses, and toxicology to provide recommendations to the research chemist or engineer regardingthe environmental consequences of use.1. Scope1.1 This guide is intended to determine the relative envi-ronmen
5、tal influence of new munition constituents, consistentwith the research and development (R see 6.6). Exposure data can then be used with othertoxicological data collected from previous stages in a quanti-tative risk assessment to determine the relative degree ofhazard.5.2 Data developed from the use
6、 of this guide are designedto be consistent with criteria required in weapons and weaponssystem development (for example, programmatic environment,safety and occupational health evaluations, environmentalassessments/environmental impact statements, toxicity clear-ances, and technical data sheets).5.
7、3 Information shall be evaluated in a flexible mannerconsistent with the needs of the authorizing program. Thisrequires proper characterization of the current problem. Forexample, compounds may be ranked relative to the environ-mental criteria of the prospective alternatives, the replacementcompound
8、, and within bounds of absolute environmentalvalues. A weight of evidence (evaluation of uncertainty andvariability) must also be considered with each criterion at eachstage to allow for a proper assessment of the potential foradverse environmental or occupational effects; see 6.8.5.4 This standard
9、approach requires environment, safety,and occupational health (ESOH) technical experts to determinethe risk and energetic materials researchers to evaluate theacceptability of the risk. Generally, the higher developmentalstages require a higher managerial level of approval.6. Procedure6.1 Problem Ev
10、aluationThe first step requires an under-standing of the current problem. Often, specific attributes ofexisting compounds drive the need for a replacement. Forexample, increased water solubility may indicate a propensityof the compound to contaminate groundwater. Environmentalpersistence and biomagn
11、ification may cause concerns regard-ing exposures to predatory animals and in human fish con-sumption. Increased vapor pressure may lead to significantinhalation exposures in confined spaces that would increase theprobability of toxicity to workers or soldiers. A sound under-standing of the factors
12、principally attributed to the environ-mental problem is required to focus relative evaluation of theseproperties. A conceptualization of potential exposure pathwaysgiven specific chemical properties can be helpful in ascertain-ing likelihood for adverse effects. Guide E 1689 can be helpfulin that re
13、gard. Table 1 provides stages of technical develop-ment of munition compounds and corresponding suggesteddata requirements.TABLE 1 Life-Cycle Munition Development Stage Relative to the Collection of Data Important to the Evaluation ofEnvironmental CriteriaDevelopmental Stage Action Data RequirementC
14、onception Computer modeling (QSAR), computationalchemistryChem/phys properties; toxicity estimates (mammalian and ecotoxicity)Synthesis Develop experimental chemical property data;conduct relative toxicity screenChem/phys properties (estimate fate, transport, bioaccumulation), in-vitromammalian toxi
15、city screen, in-vitro ecotoxicity screen (for example,luminescent bacteria)Testing Conduct Tier I mammalian toxicity testing Acute/subacute rodent toxicity data; in-vitro cancer screenDemonstration Conduct Tier II mammalian toxicity testing; Tier IEcotox screeningSubchronic rodent toxicity data; aqu
16、atic/plant/earthworm assaysEngineering andmanufacturing developmentCancer studiesA; Tier II Ecotox studies, evaluateplant uptakeRodent cancer evaluation; avian, amphibian studies; plant uptake modelsProduction Evaluate exposure and effects No additional data requiredBStorage and use Evaluate exposur
17、e and effects No additional data requiredDemilitarization Evaluate exposure and effects No additional data requiredAOnly necessary if in-vitro screens are predominantly positive and potential for exposure is relatively high.BIn certain cases, it may be necessary to verify predictions through environ
18、mental monitoring procedures.E25520836.2 ConceptionAt this stage of energetic material devel-opment, molecular relationships and characteristics are exam-ined to evaluate the properties of a new material. These includemolecular and electronic structure, stability, thermal properties,performance and
19、sensitivity requirements, and decompositionpathways. Since these substances are still conceptual, noempirical data exist.6.2.1 The predicted molecular and electronic structuralproperties can be used in quantitative structure-activity rela-tionship (QSAR) or other approaches to determine chemical/phy
20、sical properties relating to toxicity, fate, and transport.These properties can be gleaned from computer-modeledestimations using quantitative structure-property relationship(QSPR)-like or quantum mechanical models. The propertiesthat are useful in estimating the extent of fate and transportinclude
21、the following:6.2.1.1 Molecular weight;6.2.1.2 Water solubility;6.2.1.3 Henrys law constant;6.2.1.4 Vapor pressure;(1) Liquid-phase vapor pressure;(2) Solid-phase vapor pressure;6.2.1.5 Affinity to organic carbon; sorption (log Koc);6.2.1.6 Lipid solubility (octanol/water coefficient; log Kow);6.2.1
22、.7 Boiling point;6.2.1.8 Melting point; and6.2.1.9 Ionization potential.6.2.2 When existing materials show promise as alternatives,conduct a literature search to determine first if ChemicalAbstract Service (CAS) registry numbers are available. Acomprehensive database available from the National Inst
23、ituteof Health can be used to search for this information (http:/chem.sis.nlm.nih.gov/chemidplus/). These CAS numbers maythen be used to search for chemical/physical property valuesand toxicity information without significant risk of confusionregarding synonyms. Other databases may provide informati
24、onregarding chemical/physical properties and toxicity. See thesuite available at http:/toxnet.nlm.nih.gov/.6.2.3 Models are available to predict environmental param-eters with an inherent degree of uncertainty. It is important thatthis uncertainty be captured using a qualitative or semiquanti-tative
25、 approach (see 6.8). Examples of such models includethose found in the EPI suite3(http:/www.epa.gov/oppt/exposure/pubs/episuitedl.htm; (1)4) and can be helpful inobtaining values.6.2.4 Henrys law constant is calculated using the followingequation:H 5VpMW!S(1)where:H = Henrys law constant (atmm3/mol)
26、,Vp = vapor pressure (atm) at 25C (298 K),MW = molecular weight (g/mol), andS = solubility in water (mg substance/L).6.2.5 Octanol/water partition coefficients (log Kow) can bepredicted through the use of QSPR models. Models that predictsorption (affinity to organic carbon; log Koc) are generally no
27、trequired since log Koccan be predicted from log Kowvaluesusing the following equation:Koc5 100.078410.79191logKow!#(2)where:Koc= soil organic carbon-water partition coefficient (mLwater/g soil), andKow= n-octanol/water partition coefficient (unitless).6.2.6 QSAR approaches can also be used to estim
28、ate toxi-cological impact. Toxicity QSAR models can often predictmany parameters before experimental toxicology testing butare dependant upon similar compounds that have toxicity data.These models produce estimates of toxicity (for example, ratsubchronic no observed adverse effect levels (NOAELs) ar
29、eused to rank new energetic materials, not to evaluate themquantitatively. These methods provide a relatively fast, low-cost method for developing the minimum amount of environ-mental data necessary for an initial evaluation of environmen-tal impacts. They can be used as a basis for go/no-go decisio
30、nsregarding further development and can serve to focus furtherresearch. These rankings shall be based on measures of toxicity(for example, acute values such as LD50s, chronic/subchronicrat lowest observed adverse effect levels (LOAELs), and soforth). QSARs may also be used in a qualitative sense toe
31、valuate the need for focused developmental, reproductive (forexample, endocrine-like functional groups) in vivo testing.Compounds with structure suggesting specific toxicity shouldbe qualified for further testing at advanced stages in munitiondevelopment (for example, engineering and manufacturingde
32、velopment).6.2.7 Following the problem evaluation procedure, pertinentproperties are compared along with those of other candidatesubstances and, if applicable, with the currently used munitionconstituent marked for replacement. Estimates of the relativelevel of confidence (for example, high, medium,
33、 or low) shallalso be assigned to each attribute. These qualifiers may beassigned a numerical weight and used in a semiquantitativeapproach. These substances are then ranked, evaluated basedon absolute parameters, and/or assessed relative to the replace-ment substance configuration according to thes
34、e criteria toprovide the munition scientist with a prioritized list from whichto focus efforts or provide general recommendations regardingtheir use in an environmental or occupational context or both.6.3 SynthesisFollowing the conceptualization and suc-cessful assessment of a new material, it must
35、be made. Once itis shown that small amounts of a new energetic material can beproduced, small-scale screening tests shall be performed toestablish performance characteristics. If the material is foundto be acceptable from a performance perspective, risks from anenvironmental and occupational perspec
36、tive can be morereliably determined through experimentally determiningchemical properties in small-scale tests using actual material. Ifthe candidate is suitable for further consideration, performance3EPI Suite is a trademark of ImageWare Systems, Inc. 10883 Thornmint RoadSan Diego, CA 92127.4The bo
37、ldface numbers in parentheses refer to the list of references at the end ofthis standard.E2552084in gun or warhead configurations will be modeled to provideinformation on emissions.Amounts needed for each assay mayneed to be determined before initiation. These methods can beused to develop data that
38、 can increase confidence in risk (fate,transport, and toxicity) predictions. In addition, analyticalchemistry methods are also needed at this stage.6.3.1 Analytical chemistry and standard experimental meth-ods can be used to develop the following data. The appropriateASTM International standard is r
39、eferenced where applicable.6.3.1.1 Water SolubilityTest Method E 1148.6.3.1.2 Vapor PressureTest Method E 1194.6.3.1.3 Log KocTest Method E 1195.6.3.1.4 Log KowTest Method E 1147.6.3.1.5 Boiling PointOrganization for Economic Coop-eration and Development (OECD) Test Guidelines 102 (2).6.3.1.6 Relati
40、ve ToxicityUse of in vitro techniques.6.3.2 Increased water solubility suggests a propensity forincreased bioavailability and transfer to groundwater. This,however, shall be compared with the affinity to organic carbon,since sorption assists in retarding migration to groundwater.Asmentioned, log Kow
41、values may be derived from log Kocvalues(3); however, experimentally derived data are recommended atthis stage, if feasible.6.3.3 Increased vapor pressure and a lower boiling pointsuggest a greater propensity for inhalation exposures and canbe compared in a relative sense. Molecular weight is valuab
42、lein determining exposure within and between organ systems (4,5).6.3.4 Relative acute toxicity can be evaluated using low-cost and rapid in-vitro basal cytotoxicity assays (for example,Neutral Red Uptake (NRU) http:/iccvam.niehs.nih.gov/methods/invitro.htm). Relative acute toxicity can be evaluatedu
43、sing relatively low-cost in-vitro cell culture techniques (forexample, MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell exclusion dyes, andpropidium iodide (6, 7). Specific assays that assess cellularfunction may be needed when toxicity for replacement com-pound is not me
44、diated by changes in metabolism, necrosis orcell death. Screening-level ecotoxicological methods (8), TestMethod D 5660) can be used to ascertain relative toxicity to thetest organism and can be used for ranking purposes, though allhave limitations (8, 9).6.3.5 As before, these data are used to impr
45、ove on theinformation and confidence estimates used in the previousevaluation. The relative weight of each ranking criteriondepends upon the factors most important to the initial problem.Confidence estimates shall be used as ranking criteria inproviding the hierarchical list of candidates.6.4 Testin
46、gThis involves testing new energetic materialsin various systems and configurations to determine the bestformulations to achieve specific performance characteristics.This often requires varying the proportions of various com-pounds to achieve performance goals. Other substances, suchas binders or pl
47、asticizers, are used to meet specifications. Thisrequires an understanding of the dynamics of these mixturesinsofar as they affect transport and fate (for example, productsof combustion) as well as attributes of any introduced com-pounds to the mixture. Since larger masses/volumes of com-pounds are
48、needed at this stage, the probability for humanexposure increases; therefore, it is important to have baselinehuman toxicity data (Tier I testing).At this stage, the followingare important data to collect.6.4.1 Sorption can be measured experimentally in varioussoil types using Test Method E 1195. Mo
49、deled approachesusing available software systems could be used to estimatebiodegradation, persistence, bioaccumulation, and toxicity,respectively (1).6.4.2 Animal data are now needed since potential for humanexposure is likely. Acute rodent studies shall be conductedbefore subacute and subchronic studies. Test Method E 1163describes the up/down method to determine the lethal dose for50 % of rats exposed to a single oral dose. Following thedetermination of the acute LD50, a 14-day range finding(subacute) study is required to refine sublethal levels ofexposure fo
