Small Business Administration (SBA) Comments on the Interagency Science Consultation Draft IRIS
Assessment of Trimethylbenzenes June 2016 (Date Received: June 29, 2016)
SBA Office of Advocacy - June 29, 2016 - Comments on TMB - Step 6B Version
Response to Public Comments:
EPA surprisingly failed to respond to major public comments that were included in Step 5. EPA
explains in its IRIS slides that Step 5 includes comments made in the Step 5 process (comments
made to the CAAC and the Chartered SAB on the peer-reviewed draft assessment). It states:
The draft assessment is revised to reflect the peer review comments, public comments, and
newly published studies that are critical to the conclusions of the assessment. The disposition
of peer review comments and public comments becomes part of the public record.
https://www.epa.gov/sites/production/files/2014-03/documents/iris_process_flow_chart.pdf
EPA, instead, provides only responses to initial public comments on the external review draft
(ERD). The new enhanced IRIS procedures do not suggest that later public comments can be
ignored by EPA. Please provide a response to the major public comments not yet addressed.
The NRC recommended a major increase in clarity and transparency, and the response to public
comments was a major part of the plan designed by EPA to address those recommendations.
Among the major comments that should be addressed are : (1) the assessment needs to take
into account the September 2014 final rule published by the Office of pesticide Programs (OPP)
determining that complex C9 aromatics pose no appreciable risks to the general population, and
(2) the assessment needs to address the inconsistency in the derived RfD values between NCEA
and OPP.
Preamble Comments Regarding Public and Interagency Comment Procedures:
Current Draft Final Preamble Page xxxvii
Step 4: Public comment, followed by external peer review. The public reviews the draft
assessment. IRIS program scientists address the public comments, then release a revised draft
for independent external peer review. The peer reviewers consider whether the draft
assessment assembled and evaluated the evidence according to EPA guidance and whether the
evidence justifies the conclusions.
Step 5: Revise assessment. IRIS program scientists revise the assessment to address the
comments from the peer review.
Step 6: Final agency review and interagency science discussion. The IRIS program
discusses the revised assessment with EPA's program and regional offices and with other
federal agencies and the Executive Office of the President.

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Peer Review Draft Preamble (Deleted Text) Page xxi:
Step 4. Public review and comment, followed by external peer review. The EPA releases the
draft assessment for public review and comment. A public meeting provides an opportunity to
discuss the assessment prior to peer review. Then the EPA releases a draft for external peer
review. The peer review meeting is open to the public and includes time for oral public
comments. The peer reviewers assess whether the evidence has been assembled and
evaluated according to guidelines and whether the conclusions are justified by the evidence.
The peer review draft, written public comments, and peer review report become part of the
public record.
Step 5. Revision of draft Toxicological Review and development of draft IRIS
summary. The draft assessment is revised to reflect the peer review comments, public
comments, and newly published studies that are critical to the conclusions of the
assessment. The disposition of peer review comments and public comments becomes part
of the public record.
Step 6. Final EPA review and interagency science discussion with other federal
agencies and the Executive Offices of the President The draft assessment and summary
are revised to address the EPA and interagency comments. The science discussion draft,
written interagency comments, and EPA's response to major comments become part of the
public record.
EPA should return to the previous version of the preamble. It more accurately captures the
steps and is more specific regarding transparency - including the discussion of the interagency
and public comments, and the response to major comments becoming part of the record. In the
revised Step 6B version, EPA is no longer required to respond to the Step 5 public comments.
Furthermore, EPA is no longer required to respond to major interagency comments in Step 6.
Lastly, EPA should specifically state that it will respond to the initial public comments on the ERD
in Step 4. Now, it simply says in Step 4 that "IRIS program scientists address the public
comments." Does this mean address these comments in the body of the new draft assessment
text released for peer review, or a separate response to comments document? In the case of
TMB, EPA did release the response to comments in Step 5. Why does it state that this occurs
instead in Step 4 now?
l. Preamble Page xxxvi (redline) - extrapolation of slope factors
Here is the excerpt from the EPA Cancer Guidelines:
A nonlinear extrapolation method can be used for cases with sufficient data to ascertain the
mode of action and to conclude that it is not linear at low doses but with not enough data to
support a toxicodynamic model that may be either nonlinear or linear at low doses. Nonlinear
extrapolation having a significant biological support may be presented in addition to a linear

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approach when the available data and a weight of evidence evaluation support a nonlinear
approach, but the data are not strong enough to ascertain the mode of action applying the
Agency's mode of action framework. If the mode of action and other information can support
chemical-specific modeling at low doses, it is preferable to default procedures.
The preamble makes use of only the first sentence which refers to the use of a reference value
approach. However, it omits the second sentence which advises the use of alternative
approaches under less certain circumstances, i.e. when there is "significant biological support".
This issue comes up very frequently and is the subject of substantial criticism when the
alternative model is omitted. This second sentence should be included in the preamble. EPA
should not be modifying the current policy by omission.
2.	Preamble Page xxxv - Selection of Studies for Derivation of Toxicity Values
The preamble states:
"Studies of low sensitivity tend to underestimate toxicity and may be less useful."
EPA provides no basis for the statement that these studies "may be less useful", and should be
deleted.
See below the utility of such studies as stated in the Cancer Guidelines.
The 2005 Cancer Guidelines also provide:
"Studies of inadequate sensitivity where an adequately high dose has not been reached may be
used to bound the dose range where carcinogenic effects might be expected." Page 2-19
Also, it is not clear to us that studies of low sensitivity tend to underestimate toxicity. Perhaps,
EPA should delete this entire sentence.
3.	Preamble Page xxix- Integrating the Evidence of Causation
The preamble states:
"Each synthesis considers aspects of an association that may suggest causation: consistency,
exposure-response relationship, strength of association, temporal relationship, biological
plausibility, coherence, and "natural experiments" in humans..'
In comparison to the 2005 Cancer Guidelines, EPA has omitted the concept of "specificity of the
observed association" - please include in this comprehensive list. Better yet, the earlier text in

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the peer reviewed version, which appears to have been copied from the Cancer Guidelines, may
be preferable. The SAB objected to EPA making statements that were inconsistent with the EPA
guidance, but not referencing or using the guidance.
4. Preamble - General Comment
The draft would be improved by adding back the citations to existing EPA guidance, and not
relying solely on referring to the Handbook that doesn't yet exist, and is subject to change.

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