ASTM E2552-2016 Standard Guide for Assessing the Environmental and Human Health Impacts of New Compounds for Military Use《用于评估军事用新化合物的环境和人类健康影响的标准指南》.pdf

1、Designation: E2552 16Standard Guide forAssessing the Environmental and Human Health Impacts ofNew Compounds for Military Use1This standard is issued under the fixed designation E2552; the number immediately following the designation indicates the year oforiginal adoption or, in the case of revision,

2、 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. Researcheffo

3、rts are underway to identify new substances that have negligible environmental impacts andimplement them in military weapon systems and applications. This guide is intended to provide astandardized method to evaluate the potential human health and environmental impacts of prospectivecandidate substa

4、nces. This guide is intended for use by technical persons with a broad knowledge ofrisk assessment, fate and transport processes, and toxicology to provide recommendations to theresearch chemist or systems engineer regarding the environmental consequences of use.1. Scope1.1 This guide is intended to

5、 determine the relative envi-ronmental influence of new substances, consistent with theresearch 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

6、developed 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 techn

7、ical data 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

8、 replacementcompound, 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.

9、8.5.4 This standard approach requires environment, safety,and occupational health (ESOH) technical experts to determinethe magnitude of the hazard and system engineers/researchersto evaluate the acceptability of the risk. Generally, the higherdevelopmental stages require a higher managerial level of

10、approval.6. Procedure6.1 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. E

11、nvironmentalpersistence 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 troops. A sou

12、nd under-standing of the 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. Guid

13、e E1689 can be helpfulin 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

14、of a new material. Theseinclude 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 structuralproperti

15、es can be used in quantitative 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)-lik

16、e or quantum mechanical 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;E2552 1636.2.1.4 Vapor pressure;(1) Liquid-phase vapor pressure;(2) Solid-phase vapor pressu

17、re;6.2.1.5 Affinity to organic carbon; sorption (log Koc);6.2.1.6 Lipid solubility (octanol/water coefficient; log Kow);6.2.1.7 Boiling point;6.2.1.8 Melting point; and6.2.1.9 Ionization potential.6.2.2 When using existing materials, conduct a literaturesearch to determine first if Chemical Abstract

18、 Service (CAS)registry numbers are available. A comprehensive databaseavailable from the National Institute of Health can be used tosearch for this information (http:/chem.sis.nlm.nih.gov/chemidplus/). These CAS numbers may then be used to searchfor chemical/physical property values and toxicity inf

19、ormationwithout significant risk of confusion regarding synonyms.Other databases may provide information regarding chemical/physical properties and toxicity. See the suite available athttp:/toxnet.nlm.nih.gov/.6.2.3 Models are available to predict environmental param-eters that can be useful in pred

20、icting environmental fate andtransport with an inherent degree of uncertainty. It is importantthat this uncertainty be captured using a qualitative or semi-quantitative approach (see 6.8). Examples of such modelsinclude those found in the EPI suite4(http:/www.epa.gov/oppt/exposure/pubs/episuitedl.ht

21、m; (1)5) 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),Vp = vapor pressure (atm) at 25C (298 K),MW = molecular weight (g/mol), andS = solubility in water (mg substance/L).6.2.5 Octanol/w

22、ater partition coefficients (log Kow) can bepredicted through 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= so

23、il 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 estimate toxi-cological impact. Toxicity QSAR models can often predictmany parameters before experimental toxicology testing butare depen

24、dent upon similar compounds that have toxicity data.These 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

25、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 decisionsregarding further development and can serve to focus furtherresearch. These rankings shall be based on measures of toxicity(for ex

26、ample, acute values such as LD50s, chronic/subchronicrat lowest 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 wi

27、th structure suggesting specific toxicity shouldbe qualified 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 candidatesub

28、stances and, if applicable, with the currently used constitu-ents marked for replacement. Estimates of the relative level ofconfidence (for example, high, medium, or low) shall also beassigned to each attribute. These qualifiers may be assigned anumerical weight and used in a semiquantitative approa

29、ch.These substances are then ranked, evaluated based on absolute4EPI 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 ofthis standard.TABLE 1 Life-Cycle Munition Development Stage R

30、elative to the Collection of Data Important to the Evaluation ofEnvironmental CriteriaDevelopmental Stage Action Data RequirementConception Computer modeling (QSAR), computationalchemistryChem/phys properties; toxicity estimates (mammalian and ecotoxicity)Synthesis Develop experimental chemical prop

31、erty 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 toxicity testing Acute/subacute rodent toxicity data; in-vitro

32、 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, evaluateplant uptakeRodent cancer evaluation; avian, amphibian

33、 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 requiredAOnly necessary if in-vitro screens are predominantly p

34、ositive and potential for exposure is relatively high.BIn certain cases, it may be necessary to verify predictions through environmental monitoring procedures.E2552 164parameters, and/or assessed relative to the replacement sub-stance configuration according to these criteria to provide thesystem in

35、vestigator with a prioritized list from which to focusefforts or provide general recommendations regarding their usein an environmental or occupational context or both.6.3 SynthesisFollowing the conceptualization and suc-cessful assessment of a new material, it must be made. Once itis shown that sma

36、ll 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 perspective can be morereliably determin

37、ed through experimentally determiningchemical 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 deter

38、mined before initiation. These methods can beused 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 devel

39、op the following data. The appropriateASTM International 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-era

40、tion and Development (OECD) Test Guidelines 102 (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. Thisparameter is also useful in predicting oral, inhalation, anddermal bioavailabil

41、ity and toxicity. This property, however,shall be compared with the affinity to organic carbon, sincesorption assists in retarding migration to groundwater. Asmentioned, log Kowvalues may be derived from log Kocvalues(3); however, experimentally derived data are recommended atthis stage, if feasible

42、.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 valuablein determining exposure within and between organ systems (4,5).6.3.4 Relative acute toxicity can be evaluated using low-c

43、ost 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 evaluatedusing relatively low-cost in-vitro cell culture techniques (forexample, MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo

44、lium 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 mediated by changes in metabolism, necrosis orcell death. Screening-level ecotoxicological methods (8), TestMethod D5660) can

45、 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 improve on theinformation and confidence estimates used in the previousevaluation. The relative weight of each ranking criterion

46、depends 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 TestingThis involves testing new materials in varioussystems and configurations to determine the best formulationsto achieve speci

47、fic performance characteristics. This oftenrequires varying the proportions of various compounds toachieve performance goals. Other substances, such as bindersor plasticizers, are used to meet specifications. This requires anunderstanding of the dynamics of these mixtures insofar asthey affect trans

48、port and fate (for example, products of com-bustion) as well as attributes of any introduced compounds tothe mixture. Since larger masses/volumes of compounds areneeded at this stage, the probability for human exposureincreases; therefore, it is important to have baseline humantoxicity data (Tier I

49、testing). At this stage, the following areimportant data to collect.6.4.1 Sorption can be measured experimentally in varioussoil types using Test 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 and a higher degree of certainty is needed.Acute rodent studies shall be conducted before subacute andsubchronic studies. Test Method E1163 describes the stagewiseprobit metho