### December

**1 3, 2013**  **GENERAL**

**COMMENTS AT** 

**T HE EP**  **A BI** **- MONTHL** 

**Y LISTENING SESSION: RDX, ETBE,**  **and tert** **- Butanol**  **O n behalf of**  **ACC and**  **the Center for**  **A dvancing Risk**  **Assessment Science**  **and Policy Nancy Beck,**  **PhD, DABT Senior**  **Dir ector**  **, ACC** 

# If the same person says the same thing three times, does this create a weight of evidence ?

## ACC and **the Center f**  **or A**  **dvancing Risk**  **Assessment Science**  **and Policy (ARASP)**  **ACC:**

• Represents the leading companies engaged in the business of chemistry
. • Committed to improved environmental, health and safety performance through Responsible Care ®



### . 

## ARASP:

• Coalition of 19 organizations focused on development and application of scientifically sound methods for conducting chemical assessments.

• Members include chemical specific panels and other trade associations. See : http://arasp.americanchemistry.com/

## IRIS Enhancements  July 2013 IRIS enhancements are a constructive step forward.  Early stakeholder engagement, particularly before a draft is developed will help strengthen assessments and move them to completion in a more timely manner
.  Planning and scoping will help in understanding parameters that will be assessed.  Complex scientific issues will ideally be discussed earlier in the process.  Identification of critical studies and their summaries should help stakeholders understand the direction the agency is heading.  Appropriate exposure response tables will help provide context
. 

###  The release of evidence tables, while a helpful start, is not suf ficiently consistent with the IRIS enhancements.  Further improvements are necessary.

## IRIS Pr**ocess Step 1**   The revised IRIS process documentation includes the following in the details about Step 1:  Begins with planning and scoping, including public meeting on technical problem f orm ulation and release of planning and scoping summary. 1⁄2 Conducts literature search and critical study selection
.  Develops evidence tables that succinctly summarize the critical studies to be considered in developing the assessment .  Publicly releases literature search, literature search strategy , critical study selection criteria, evidence tables for critical studies, and exposure
response figures (which graphically depict responses at dif ferent exposure levels for studies in evidence tables ). 1⁄2 Convenes public meeting to discuss literature search, evidence tables, exposure - response figures, and key issues
. 

###  Step 1 elements are not completed in the RDX, tert - butanol and ETBE releases.

## Evidence **Ta ble**  **Releases Fall**  **Short (1)**  No planning and scoping summary is provided.  There is no understanding of the questions being asked or issues to be addressed.  No context is provided in the released evidence tables.  EP A’ s definition of a systematic review is related only to the literature search.  Docum ent entitled “Systematic review of the ETBE literature” on IRIS takes readers to a HERO webpage for identified studies.  Systematic review must be more than a first step literature search strategy.  All studies identified in the literature search, that provide an endpoint where a change is seen, are deemed ‘critical studies’.  There are no ‘critical study’i dentification criteria.  Study quality must be an essential element of ‘critical study’ identification.

## Evidence **Ta ble**  **Releases Fall**  **Short (2)**  Evidence tables present all studies that show a change in an endpoint, not necessarily ‘critical studies’.  There is no discussion of which studies should be treated as ‘critical studies’due to quality

, methodology

, adversity of ef

fect, or any other criteria.  Studies negative for statistical changes are excluded from evidence tables, therefore making them incomplete and misleading.  While an approach like this may work where there are limited studies identified in a literature review , as more complex chemicals are reviewed, the EP A approach will be unworkable
.  Burden is on stakeholders to review and comment on every study identified in the literature review , not just those in the table
. 

###  Evidence tables focus only on endpoints, ignoring all ‘critical studies’that relate to mode of action (MOA) only
.

## Evidence **Ta ble**  **Releases Fall**  **Short (3)**  Exposure
- response arrays are misleading  All studies are treated as being of equal quality , when this is not the case.  Exposure
- response arrays are limited to positive endpoints, ignoring studies with negative endpoint findings and also ignoring all mode of action information.

## Impr**oving Evidence**  **Ta bles**  1) Release planning and scoping summary along with evidence tables. 2) Don’ t confuse a literature search with a systematic review. Clarify terminology and use it consistently
. 3) Determine, a priori , criteria for ‘critical study’ identification. This should include not only endpoint specific data, but also mode of action information.

• It should be more specific than including all relevant studies identified in the literature review
. 4) Critical study criteria should include, at a minimum, a review of study quality, methodology, relevance, and adversity of ef fect (if relevant).

• This review should be released by EP A along with the evidence tables. 5) Evidence tables and exposure
- response arrays should be developed for mode of action information (see Kushman et. al., for example). 6) Exposure
- response arrays should include only those studies of suf ficient quality (e.g. those meeting critical study criteria) and quality of studies should be clear in the arrays.

# Thank **Yo u!**   EP A has taken a strong first step. However improvements are needed.  Consistency with intent of IRIS process enhancements will go a long way towards improving the evidence tables.  Most importantly

, EP A must conduct a review of the quality and relevance of studies before moving them forward as ‘critical studies’ for an IRIS assessment.  Wi thout changes and improvements, the utility of evidence tables, following the current structure, may not help suf ficiently speed the finalization of IRIS assessments.  **Small changes, such as those noted in our general**  **re commendations**  **slide will lead to much impr ovement.** 

# Knowing is not enough; we must apply
. Wi lling is not enough; we must do
.

- Johann Wo lfgang von Goethe

# Knowing is not enough; we must apply
. Wi lling is not enough; we must do
.

- Johann Wo lfgang von Goethe