Page 1 of 2Department of Defense Comments on theNCEA Proposed Draft SAB Peer Review Charge Questions for DioxinComments submitted by: Robert BoydOrganization: Department of DefenseDate Submitted: 13 April 2010*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E);or Other (O). Also please indicate if Major i.e. affects theoutcome, conclusions or implementation of the assessment.CommentNo.SectionPage &Paragraph orGlobalCommentSuggested Action, Revisionand References (if necessary)Category*1 Global NCEA’s response document discusses modelingboth animal data and epidemiological data, eventhough only the epidemiological data are used forquantitative analyses of toxicity values. As thecurrent charge questions take 6 pages, and will takea considerable amount of time by the review panel,we suggest that the questions involving analysesthat are not used directly to develop either cancerpotency factors or reference values be eliminated.If EPA believes that the animal data isimportant for an understanding of the humanhealth assessment it would be helpful if thethose charge questions reflected thissignificance, otherwise we recommend thatEPA consider eliminating the questions relativeto animal data to better focus the efforts of thepanelS2 Section 3;1.c.With regard to EPA’s modification of the publishedPBPK model, the question is not clear as to whetherEPA wants comments on the changes made orwhether it is appropriate to modify a published,peer-reviewed model without having themodifications peer reviewed. This question isespecially relevant as (1) EPA states that theirmodifications made little difference in thequantitative results (although they do not presentthe results of the unmodified model) and (2) themodel was developed by EPA laboratory scientistsand modelers, i.e., this part of EPA is substitutingtheir judgment for that of EPA scientists whodeveloped the data and the model.As both questions are relevant, we suggestmodifying the question to read: “c. Whetherthe modifications implemented by EPA to thepublished Emond et al. model are appropriatefor the analysis and whether suchmodifications should be externally peerreviewed prior to their use in a regulatoryanalysis such as this.”S3 Section 5. 1 As presented, the SAB panel membersare likely toinfer that only one descriptor may be used perchemical. EPA’s 2005 cancer guidelines, however,clearly state (and give examples) that severaldescriptors may be applied to one chemical. In thiscase, we suggest that the reviewers be given theoption (as one of the examples in EPA’s cancerguidelines) of different descriptors for differentintensities of exposure.Recommend adding the following sentencesafter the last sentence: “EPA’s cancerguidelines also allow different descriptors fordifferent exposure levels. Do the data andweight of the evidence suggest that very high,acute exposures should be “known humancarcinogen” and low, chronic exposures shouldbe “likely to be carcinogenic to humans”?S/MPage 2 of 2Department of Defense Comments on theNCEA Proposed Draft SAB Peer Review Charge Questions for DioxinComments submitted by: Robert BoydOrganization: Department of DefenseDate Submitted: 13 April 2010*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E);or Other (O). Also please indicate if Major i.e. affects theoutcome, conclusions or implementation of the assessment.CommentNo.SectionPage &Paragraph orGlobalCommentSuggested Action, Revisionand References (if necessary)Category*4 Section 5.7.b.EPA did not develop one OSF, but presents severalrisk-specific slope factors. As this is a procedurethat has not been done before, it is important to askthe reviewers if they are relevant for the use andconsistent with current guidance and policy.Moreover, as other questions ask whether thisprocedure follows EPA’s cancer guidelines, wesuggest that this issue be addressed, as thisprocedure is not consistent with the guidelines.Add the following to the end of 7.b: “EPA’s2005 Cancer Guidelines” state that, if the doseresponse curve is nonlinear a low doses (evenif it is nonlinear with no threshold), theextrapolation below the point of departureshould use the reference dose procedure.Does this derivation of dose-dependent OSFsfollow the cancer guidelines? Also, is the useof these multiple, risk-specific OSFs, clear,?”S/M5 Section 5.10 The NAS panel recommended a threshold doseresponse model to characterize dioxin’scarcinogenicity. The questions listed in #10 do notdirectly address this issue.Recommend adding a question in #10 thatasks whether EPA gave appropriateconsideration to nonlinear approaches per theNAS recommendation.S/M6 Section 5. 10 NCEA’s response document models nonlinearextrapolations for the animal models but usesepidemiological data to derive its OSFs. EPA’scancer guidelines indicate that the same point ofdeparture should be used for both the linear andnonlinear extrapolations to low doses. Therefore,the correct comparison should be for those two, andthis should be reflected in the charge questions.Add the clause in bold to the third sentence:“Are there other nonlinear approaches,including the one specified by EPA’s 2005Cancer Guidelines,that could be readilydeveloped based on existing data for theassessment of TCDD carcinogenicity?”Also add the following at the end: “EPA’s 2005Cancer Guidelines specify that, when there aresufficient data to indicate that at low doses thedose-response curve is nonlinear, an RfDapproach should be used from the point ofdeparture. As NCEA has determined a point ofdeparture for its OSFs, should one or more ofthese be used for an RfD approach forestimating low-dose cancer risks?”S/M