IRIS STEP 6 INTERAGENCY COMMENTS (DOD)Department of Defense Comments on theDraft Final IRIS Toxicological Assessment for InorganicArsenic Toxicological Assessment, Revised 09 April 2009Comments submitted by: Office of theSecretary of Defense Chemical andMaterial Risk Management DirectorateOrganization: Department of DefenseDate Submitted: 15 May 2009*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(enter“Global” ifreportsection-wide)CommentSuggested Action, Revisionand References (if necessary)Category*1.GlobalGlobalWe are satisfied with the U.S. EPA’s response tocomments from DOD on the previous (2008)version of this arsenic toxicological assessment. Wealso wish to acknowledge the improvements that theU.S. EPA authors have made in updating significantportions 2008 draft in response to the U.S. EPAScience Advisory Board (SAB) (Appendix A) andother peer reviewer’s comments andrecommendations.No suggested action required.O2.Section 5.3.1,“Background:History ofCancer RiskAssessmentsfor Arsenic.”Page 98New text on page 98 states that “The Office ofPesticide Programs (OPP) also recently appliedcancer slope factors based on the U.S. EPA (2001)assessment in their Reregistration EligibilityDecision (RED) Documents for organic arsenicpesticides (U.S. EPA, 2006c) and for InorganicArsenicals and/or Chromium Based WoodPreservatives (U.S. EPA, 2008).”It would be useful to compare the key assumptionsand conclusions from the U.S. EPA OPP’stoxicological assessment related to inorganicarsenic’s carcinogenicity to this assessment insupport of U.S. EPA’s IRIS program.Consideration should be given to providingadditional information for comparisonpurposes between the two inorganic arseniccarcinogenicity assessments, if feasible andtime permits.S3.Section 5.3.1.“Background:Pages 103,104New analysis was included in the assessment usinga modified version of the “BEIR IV” relative riskConsider, discussing how factors, such aspotential genetic differences, lifestyle (forSIRIS STEP 6 INTERAGENCY COMMENTS (DOD)Page of 52Department of Defense Comments on theDraft Final IRIS Toxicological Assessment for InorganicArsenic Toxicological Assessment, Revised 09 April 2009Comments submitted by: Office of theSecretary of Defense Chemical andMaterial Risk Management DirectorateOrganization: Department of DefenseDate Submitted: 15 May 2009*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(enter“Global” ifreportsection-wide)CommentSuggested Action, Revisionand References (if necessary)Category*History ofCancer RiskAssessmentsfor Arsenic.”model, and is described in Appendix E. A keyassumption underlying this model is that “...the riskof arsenic-related cancer mortality or incidence forthe U.S. population is a constant multiplicativefunction of the current background age profile ofcancer risks in the same U.S. population.”The text does not discuss how factors, such aspotential genetic differences, lifestyle (for example,smoking history), and cumulative exposures to otherpotentially carcinogenic materials may impact thevalidity of this key assumption.example, smoking), and cumulative exposuresto other potentially carcinogenic materials mayimpact the validity of this key assumption andhow these variations could impact thequantitative risk assessment.4.Section 5.3.4.“Selection ofCancerEndpoints andEstimation ofRisks for U.S.Populations.”Page 107,108New text included in this section states, “The ED01and LED01values are estimated using a variation onthe “BEIR IV” model derived for use in estimatingpopulation cancer risks for radionuclide exposures(NRC, 2001). This method, which is describedfurther in Section 5.3.7.3 and Appendix E.2,includes the application of relative cancer riskestimate derived from the Taiwanese dose-responseassessment multiplicatively to age-specific cancerrisks for the U.S. In this model, the backgroundhazard consists of age-specific cancer incidenceAgain, we recommend that the text shoulddiscuss the potential impact of differences inlifestyles between the U.S. and Taiwanesepopulations (for example, smoking history;access to better medical treatment, etc. havingan impact on cancer survival rates.SIRIS STEP 6 INTERAGENCY COMMENTS (DOD)Page of 53Department of Defense Comments on theDraft Final IRIS Toxicological Assessment for InorganicArsenic Toxicological Assessment, Revised 09 April 2009Comments submitted by: Office of theSecretary of Defense Chemical andMaterial Risk Management DirectorateOrganization: Department of DefenseDate Submitted: 15 May 2009*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(enter“Global” ifreportsection-wide)CommentSuggested Action, Revisionand References (if necessary)Category*data for bladder and lung cancer from the UnitedStates for the years 2000-2003 (NCI, 2006). Theratios of cancer mortalityto incidence for arsenicrelated cancers are assumedto be the same in theU.S. and Taiwanese populations.”The text does not discuss the impact of differencesin lifestyles (for example, smoking history; access tobetter medical treatment, etc.) having an impact oncancer survival rates.5Section 5.3.5.“Non-WaterArsenic Intakeand DrinkingWater.”Page 108.The U.S. EPA assessment used 10 μg/day non-waterdietary intake in the baseline analysis for both theexposed and reference populations in southwestTaiwan. Page 108, which states that “It does notinclude the arsenic intake value from water used forcooking rice or produce, which was addressedseparately via sensitivity analysis modeling withhigher water intake values...” This newinformation helps clarify what constituted “nonwater arsenic,” which had been an area of concernrelated to water used for cooking potentiallycontributing to a higher inorganic arsenic intakethan 10 ug/l.No suggested action required.SIRIS STEP 6 INTERAGENCY COMMENTS (DOD)Page of 54Department of Defense Comments on theDraft Final IRIS Toxicological Assessment for InorganicArsenic Toxicological Assessment, Revised 09 April 2009Comments submitted by: Office of theSecretary of Defense Chemical andMaterial Risk Management DirectorateOrganization: Department of DefenseDate Submitted: 15 May 2009*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(enter“Global” ifreportsection-wide)CommentSuggested Action, Revisionand References (if necessary)Category*6.Section 5.3.7.“RiskAssessmentMethodology.”” Section5.3.7.3.“Estimation ofLED01ValuesUsing RelativeRisk Models.”Section5.3.8.2.“Comparisonto PreviousCancer RiskEstimates.”U.S. EPA“Response toOMBComment TR5.3.7.2,” Page16, datedMarch 2009.Pages 111,114, 117-119.Page 111 states that “U.S. bladder and lung cancerincidence data for the years 2000-2003 (NCI[National Cancer Institute] (2006) were used as thereference values for calculating U.S. lifetime cancerrisks. Thus, the LED01values are expressed interms of lifetime cancer incidence for the U.S.population (see Section 5.3.7.3).”Page 118 text states that, “In the analyses thatfollow, some of the risk comparisons are based onmortality estimates that have been converted toincidence using recent U.S. incidence-mortalityratios. This conversion introduces additionaluncertainty into the comparisons; different resultswould have been obtained had the incidence beenmodeled directly rather than estimated after thefact.”The “Response to Comment” states that “Adoptionof more recent background U.S. mortality andcancer incidence data may have resulted in thecurrent risk estimates being about 50% increasedcompared to what the would have been if older datahad been used.” This more quantitative comparisonwould be useful to include in Section 5.3.8.2.We recommend including this morequantitative comparison in Section 5.3.8.2.S