Department of Defense Comments on the 

Draft External Peer Review Charge for Methanol 

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

Organization: Department of Defense Date Submitted: 20 Novembe

*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

1 A.1. We would prefer that the text “objectively and” be 

retained. 

Please retain “objectively” exquestion. 

2 B.1.& 2 Several recent NAS reports have recommended that 

risk assessments move from the historical practice of selecting one critical study to represent the quantitative analysis. It might be useful to ask the reviewers if they believe the results of the three analyses should be combined, and if so, how would they recommend that they be combined. 

Suggest adding to the questiorecommend that the results frostudy should be used quantitaresponse assessment, and if sotechniques would you recommaccomplish combine or comp

3 B.3. first 

bullet 

Some of the “subtraction from background” included a time-dependant change. We recommend that this adjustment be specifically called-out for review. 

We recommend that an additiadded to convey the following of the ‘subtraction from backgprocedures included a time-dei.e., because the level of methof control animals changed wthis adjustment appropriate anperformed properly?” 

4 D.3. last 

sentence. 

It is not clear whether “addressed” in the phrase “clearly described and addressed” asks the reviewers to consider if, given these issues, these data are appropriate for dose-response modeling for estimating human risks. 

We recommend changing “cleand addressed” to “...clearly appropriately selected for dosmodeling for estimation of hurisks.” 

Page 1 of 
Department of Defense Comments on the 

Draft External Peer Review Charge for Methanol 

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

Organization: Department of Defense Date Submitted: 20 Novembe

*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

5 D.4. first 

sentence 

Our interpretation of EPA’s toxicological review (TR) is that the clearance of metabolize methanol was being used as a surrogate for the production of formaldehyde or formate and that it is possible (given the values in the text) to measure formate in the blood. If this interpretation is accurate, we recommend editing the charge question to reflect these facts. 

We recommend that the questthe following manner: “If the methanol cannot be measured formaldehyde, or were not mei.e., formate, is it appropriate of metabolized methanol as a there a procedure that might pestimate from this surrogate thequivalence of the surrogate aconcentration of the metabolit

6 D.4. second 

sentence 

Our understanding from the TR is not that metabolism “may differ” among species but that metabolism in primates and rodents is known to differ. As one major difference, the TR states that metabolism is a one-step process in rodents and a two-step process in primates. 

Assuming our reading of the Twe recommend that this senteread, “The metric of formaldeis uncertain because: (1) metaare known to differ between rprimates and metabolism is a in rodents and a two-step proc[Note: we recommend both cfirst, i.e., a different enzyme, rate while the second might afi.e., requiring a function ratheof any recommended convers

Page 2 of 
Department of Defense Comments on the 

Draft External Peer Review Charge for Methanol 

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

Organization: Department of Defense Date Submitted: 20 Novembe

*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

7 D.5. and D.7 We noted that after the PBPK model was used for 

interspecies extrapolation, the risk assessors also applied the default interspecies extrapolation of BW3/4 that had already been used to derive some of the parameters for the PBPK model. We recommend that the external peer reviewers be asked to opine on this issue. 

Add the following to the end question. “Specifically, shoulequivalent dose that has been PBPK model based on clearanbe further adjusted by the ratiwas done for methanol?” 

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