IRIS STEP 6 INTERAGENCY COMMENTS (DOD) 

Department of Defense Comments on the 

Draft Final IRIS Toxicological Assessment for Inorganic Arsenic Toxicological Assessment, Revise

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 15 May 200

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

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Comment Suggested Action, R

 and References (if ne

1. Global Global We are satisfied with the U.S. EPA’s response to 

comments from DOD on the previous (2008) version of this arsenic toxicological assessment. We also wish to acknowledge the improvements that the U.S. EPA authors have made in updating significant portions 2008 draft in response to the U.S. EPA Science Advisory Board (SAB) (Appendix A) and other peer reviewer’s comments and recommendations. 

No suggested action required. 

2. Section 5.3.1, 

“Background: History of Cancer Risk Assessments for Arsenic.” 

Page 98 New text on page 98 states that “The Office of 

Pesticide Programs (OPP) also recently applied cancer slope factors based on the U.S. EPA (2001) assessment in their Reregistration Eligibility Decision (RED) Documents for organic arsenic pesticides (U.S. EPA, 2006c) and for Inorganic Arsenicals and/or Chromium Based Wood Preservatives (U.S. EPA, 2008).” It would be useful to compare the key assumptions and conclusions from the U.S. EPA OPP’s toxicological assessment related to inorganic arsenic’s carcinogenicity to this assessment in support of U.S. EPA’s IRIS program. 

Consideration should be given additional information for compurposes between the two inocarcinogenicity assessments, itime permits. 

3. Section 5.3.1. 

“Background: 

Pages 103, 

104 

New analysis was included in the assessment using a modified version of the “BEIR IV” relative risk 

Consider, discussing how factpotential genetic differences, 
IRIS STEP 6 INTERAGENCY COMMENTS (DOD) 

Page of 5 2

Department of Defense Comments on the 

Draft Final IRIS Toxicological Assessment for Inorganic Arsenic Toxicological Assessment, Revise

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 15 May 200

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

No. Section 

Page & 

Paragraph 

(enter 

“Global” if 

report 

section-wide) 

Comment Suggested Action, R

 and References (if ne

History of Cancer Risk Assessments for Arsenic.” 

model, and is described in Appendix E. A key assumption underlying this model is that “...the risk of arsenic-related cancer mortality or incidence for the U.S. population is a constant multiplicative function of the current background age profile of cancer risks in the same U.S. population.” The text does not discuss how factors, such as potential genetic differences, lifestyle (for example, smoking history), and cumulative exposures to other potentially carcinogenic materials may impact the validity of this key assumption. 

example, smoking), and cumuto other potentially carcinogenimpact the validity of this key how these variations could imquantitative risk assessment. 

4. Section 5.3.4. 

“Selection of Cancer Endpoints and Estimation of Risks for U.S. Populations.” 

Page 107, 

108 

New text included in this section states, “The ED01

and LED01 values are estimated using a variation on 

the “BEIR IV” model derived for use in estimating population cancer risks for radionuclide exposures (NRC, 2001). This method, which is described further in Section 5.3.7.3 and Appendix E.2, includes the application of relative cancer risk estimate derived from the Taiwanese dose-response assessment multiplicatively to age-specific cancer risks for the U.S. In this model, the background hazard consists of age-specific cancer incidence 

Again, we recommend that thdiscuss the potential impact olifestyles between the U.S. anpopulations (for example, smoaccess to better medical treatman impact on cancer survival r
IRIS STEP 6 INTERAGENCY COMMENTS (DOD) 

Page of 5 3

Department of Defense Comments on the 

Draft Final IRIS Toxicological Assessment for Inorganic Arsenic Toxicological Assessment, Revise

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 15 May 200

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

No. Section 

Page & 

Paragraph 

(enter 

“Global” if 

report 

section-wide) 

Comment Suggested Action, R

 and References (if ne

data for bladder and lung cancer from the United States for the years 2000-2003 (NCI, 2006). The ratios of cancer mortality to incidence for arsenicrelated cancers are assumed to be the same in the U.S. and Taiwanese populations.” The text does not discuss the impact of differences in lifestyles (for example, smoking history; access to better medical treatment, etc.) having an impact on cancer survival rates. 

5 Section 5.3.5. 

“Non-Water Arsenic Intake and Drinking Water.” 

Page 108. The U.S. EPA assessment used 10 μg/day non-water 

dietary intake in the baseline analysis for both the exposed and reference populations in southwest Taiwan. Page 108, which states that “It does not 

include the arsenic intake value from water used for 

cooking rice or produce, which was addressed separately via sensitivity analysis modeling with higher water intake values...” This new information helps clarify what constituted “nonwater arsenic,” which had been an area of concern related to water used for cooking potentially contributing to a higher inorganic arsenic intake than 10 ug/l. 

No suggested action required. 
IRIS STEP 6 INTERAGENCY COMMENTS (DOD) 

Page of 5 4

Department of Defense Comments on the 

Draft Final IRIS Toxicological Assessment for Inorganic Arsenic Toxicological Assessment, Revise

Comments submitted by: Office of the Secretary of Defense Chemical and Material Risk Management Directorate 

 Organization: Department of Defense Date Submitted: 15 May 200

*Comment categories: Science or methods (S); Editorial, grammar/spelling, clarifications needed (E); or Other (O). Also please inoutcome, conclusions or implementation of the assessment. 

Comment 

No. Section 

Page & 

Paragraph 

(enter 

“Global” if 

report 

section-wide) 

Comment Suggested Action, R

 and References (if ne

6. Section 5.3.7. 

“Risk Assessment Methodology.”” Section 5.3.7.3. “Estimation of LED01 Values 

Using Relative Risk Models.” Section 5.3.8.2. “Comparison to Previous Cancer Risk Estimates.” U.S. EPA “Response to OMB Comment TR 5.3.7.2,” Page 16, dated March 2009. 

Pages 111, 

114, 117-

119. 

 Page 111 states that “U.S. bladder and lung cancer incidence data for the years 2000-2003 (NCI [National Cancer Institute] (2006) were used as the reference values for calculating U.S. lifetime cancer risks. Thus, the LED01 values are expressed in 

terms of lifetime cancer incidence for the U.S. population (see Section 5.3.7.3).” Page 118 text states that, “In the analyses that follow, some of the risk comparisons are based on mortality estimates that have been converted to incidence using recent U.S. incidence-mortality ratios. This conversion introduces additional uncertainty into the comparisons; different results would have been obtained had the incidence been modeled directly rather than estimated after the fact.” The “Response to Comment” states that “Adoption of more recent background U.S. mortality and cancer incidence data may have resulted in the current risk estimates being about 50% increased compared to what the would have been if older data had been used.” This more quantitative comparison would be useful to include in Section 5.3.8.2. 

We recommend including this quantitative comparison in Se