1、Designation: E2552 08 (Reapproved 2014)Standard Guide forAssessing the Environmental and Human Health Impacts ofNew Energetic Compounds1This standard is issued under the fixed designation E2552; the number immediately following the designation indicates the year oforiginal adoption or, in the case o
2、f revision, the year of last revision. A number in parentheses indicates the year of last reapproval. Asuperscript epsilon () indicates an editorial change since the last revision or reapproval.INTRODUCTIONSustaining training operations while maintaining force health is vital to national security. R
3、esearchefforts 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
4、guideis intended 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 relat
5、ive envi-ronmental influence of new munition constituents, consistentwith the research and development (R see 6.6). Exposure data can then be used withother toxicological data collected from previous stages in aquantitative risk assessment to determine the relative degree ofhazard.5.2 Data developed
6、 from the use 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, toxicityclearances, and technical data
7、 sheets).5.3 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 replacem
8、entcompound, 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 Thi
9、s standard 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
10、 Problem EvaluationThe 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
11、and biomagnification 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 t
12、he factors 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 E1689 can be helpful
13、in that regard. Table 1 provides stages of technical develop-ment of munition compounds and corresponding suggesteddata requirements.6.2 ConceptionAt this stage of energetic materialdevelopment, molecular relationships and characteristics areexamined to evaluate the properties of a new material. The
14、seinclude molecular and electronic structure, stability, thermalproperties, performance and sensitivity requirements, and de-composition pathways. Since these substances are stillconceptual, no empirical data exist.6.2.1 The predicted molecular and electronic structuralproperties can be used in quan
15、titative structure-activity rela-tionship (QSAR) or other approaches to determine chemical/physical properties relating to toxicity, fate, and transport.These properties can be gleaned from computer-modeledestimations using quantitative structure-property relationship(QSPR)-like or quantum mechanica
16、l models. The propertiesthat are useful in estimating the extent of fate and transportinclude 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
17、carbon; sorption (log Koc);6.2.1.6 Lipid solubility (octanol/water coefficient; log Kow);6.2.1.7 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 ChemicalE2552 08 (2014)3A
18、bstract Service (CAS) registry numbers are available. Acomprehensive database available from the National Instituteof 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 toxic
19、ity information without significant risk of confusionregarding synonyms. Other databases may provide informationregarding 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 de
20、gree of uncertainty. It is important thatthis uncertainty be captured using a qualitative or semiquanti-tative approach (see 6.8). Examples of such models includethose found in the EPI suite4(http:/www.epa.gov/oppt/exposure/pubs/episuitedl.htm; (1)5) and can be helpful inobtaining values.6.2.4 Henry
21、s law constant is calculated using the followingequation:H 5VpMW!S(1)where:H = Henrys law constant (atmm3/mol),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 thro
22、ugh the use of QSPR models. Models that predictsorption (affinity to organic carbon; log Koc) are generally notrequired 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 s
23、oil), andKow= n-octanol/water partition coefficient (unitless).6.2.6 QSAR approaches can also be used to estimate toxi-cological impact. Toxicity QSAR models can often predictmany parameters before experimental toxicology testing butare dependant upon similar compounds that have toxicity data.These
24、models produce estimates of toxicity (for example, ratsubchronic no observed adverse effect levels (NOAELs) areused 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 n
25、ecessary for an initial evaluation of environmen-tal impacts. They can be used as a basis for go/no-go decisionsregarding 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 l
26、owest observed adverse effect levels (LOAELs), and soforth). QSARs may also be used in a qualitative sense toevaluate the need for focused developmental, reproductive (forexample, endocrine-like functional groups) in vivo testing.Compounds with structure suggesting specific toxicity shouldbe qualifi
27、ed for further testing at advanced stages in munitiondevelopment (for example, engineering and manufacturingdevelopment).6.2.7 Following the problem evaluation procedure, pertinentproperties are compared along with those of other candidatesubstances and, if applicable, with the currently used muniti
28、onconstituent marked for replacement. Estimates of the relativelevel of confidence (for example, high, medium, 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 based
29、on absolute parameters, and/or assessed relative to the replace-ment substance configuration according to these criteria toprovide the munition scientist with a prioritized list from whichto focus efforts or provide general recommendations regardingtheir use in an environmental or occupational conte
30、xt or both.6.3 SynthesisFollowing the conceptualization and suc-cessful assessment of a new material, it must 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 materia
31、l is foundto be acceptable from a performance perspective, risks from anenvironmental and occupational perspective can be more4EPI Suite is a trademark of ImageWare Systems, Inc. 10883 Thornmint RoadSan Diego, CA 92127.5The boldface numbers in parentheses refer to the list of references at the end o
32、fthis standard.TABLE 1 Life-Cycle Munition Development Stage Relative to the Collection of Data Important to the Evaluation ofEnvironmental CriteriaDevelopmental Stage Action Data RequirementConception Computer modeling (QSAR), computationalchemistryChem/phys properties; toxicity estimates (mammalia
33、n and ecotoxicity)Synthesis Develop experimental chemical property data;conduct relative toxicity screenChem/phys properties (estimate fate, transport, bioaccumulation), in-vitromammalian toxicity screen, in-vitro ecotoxicity screen (for example,luminescent bacteria)Testing Conduct Tier I mammalian
34、toxicity testing Acute/subacute rodent toxicity data; in-vitro cancer screenDemonstration Conduct Tier II mammalian toxicity testing; Tier IEcotox screeningSubchronic rodent toxicity data; aquatic/plant/earthworm assaysEngineering andmanufacturing developmentCancer studiesA; Tier II Ecotox studies,
35、evaluateplant uptakeRodent cancer evaluation; avian, amphibian studies; plant uptake modelsProduction Evaluate exposure and effects No additional data requiredBStorage and use Evaluate exposure and effects No additional data requiredDemilitarization Evaluate exposure and effects No additional data r
36、equiredAOnly 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 environmental monitoring procedures.E2552 08 (2014)4reliably determined through experimentally determiningchemical
37、properties in small-scale tests using actual material. Ifthe candidate is suitable for further consideration, performancein 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 beu
38、sed to develop data that 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 Int
39、ernational standard is referenced where applicable.6.3.1.1 Water SolubilityTest Method E1148.6.3.1.2 Vapor PressureTest Method E1194.6.3.1.3 Log KocTest Method E1195.6.3.1.4 Log KowTest Method E1147.6.3.1.5 Boiling PointOrganization for Economic Coop-eration and Development (OECD) Test Guidelines 10
40、2 (2).6.3.1.6 Relative 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.
41、Asmentioned, log Kowvalues 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. Molecu
42、lar weight is valuablein 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 toxici
43、ty can be evaluatedusing 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
44、 com-pound is not mediated by changes in metabolism, necrosis orcell death. Screening-level ecotoxicological methods (8), TestMethod D5660) 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 da
45、ta are used to improve 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 ca
46、ndidates.6.4 TestingThis 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, s
47、uchas binders or plasticizers, 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
48、 of com-pounds are 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 Tes
49、t Method E1195. Modeled 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 E1163describes 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
