Meeting Objective:
The objective of this public meeting was to obtain input from stakeholders and the public on the studies and data that will be used in these two assessments that are under development. Specifically, EPA was seeking input on preliminary materials including draft literature searches and associated search strategies, the approach for the selection of primary studies to be included in the evidence tables, the approach for evaluating methodological features of studies, evidence tables, and exposure-response arrays prior to the development of the IRIS assessments for diethyl phthalate and hexabromocyclododecane.
In response to stakeholder requests, and as discussed in the recent IRIS enhancements, EPA included scoping and planning information as part of the preliminary materials for these chemicals. This was provided for informational purposes only.
In addition, the IRIS Program was using the April meeting to explore a new format intended to promote public discussion. This new format was designed to explore varying scientific perspectives from a diverse set of stakeholders on key science issues for the two assessments in question. Stakeholders were given an opportunity to suggest additional key science issues to discuss at the meeting.
The new format was responsive to public comments heard at the IRIS December 2013 Bimonthly Public Meeting and reflects the IRIS Program’s continuing evolution in response to public comments and peer review advice. Also read the Special message from the IRIS Program that was released prior to the meeting.
Date:
The meeting was held on April 23, 2014 from 10:00 - 4:00pm Eastern Time.
Location:
The meeting was held in the EPA Conference Center at 2777 South Crystal Drive, Arlington, Virginia 22202. The meeting was also available by webinar/teleconference.
Meeting Agenda:
On April 23, 2014, EPA hosted a public meeting/webinar in Arlington, VA, to provide an opportunity for the public to give input and participate in an open discussion regarding several IRIS chemical assessments that are under development. See the final agenda:
Meeting Documents:
In March 2014, EPA released the draft literature searches and associated search strategies, evidence tables, and exposure response arrays for 2 chemicals to obtain input from stakeholders and the public prior to developing the draft IRIS assessments. Specifically, EPA was interested in comments on the following:
- Draft literature search strategies
- The approach for identifying studies
- The screening process for selecting pertinent studies
- The resulting list of pertinent studies
- Preliminary evidence tables
- The process for selecting studies to include in evidence tables
- The quality of the studies in the evidence tables
The literature search strategy, which describes the processes for identifying scientific literature, contains the studies that EPA considered and selected to include in the evidence tables. The preliminary evidence tables and exposure-response arrays present the key study data in a standardized format. The evidence tables summarize the available critical scientific literature. The exposure-response figures provide a graphical representation of the responses at different levels of exposure for each study in the evidence table.
Diethyl phthalate (DEP): James Weaver, Assessment Manager
Background. For a number of phthalates, late-gestation in-utero exposure of rats elicits a variety of effects in developing males termed the “phthalate syndrome.” These include cryptorchidism; hypospadias; decrease in anogenital distance; delayed preputial separation; agenesis of the prostate, epididymis, and vas deferens; degeneration of the seminiferous epithelium; interstitial cell hyperplasia of the testis; and retention of thoracic areolas or nipples. Effects on the female reproductive system are not typically reported, although evaluation of these endpoints is less prevalent in the experimental and epidemiological literature.
Key Science issues:
- Science issue 1. The available studies generally do not indicate that DEP induces phthalate syndrome effects in developing male rats. However, Pereira et al (2008; see Table A-4 on page A-24 of Preliminary Materials for DEP) reported effects on the male reproductive system at low exposures; although a study conducted at exposures approximately an order of magnitude higher (Fujii et al, 2005; see Table A-4 on page A-24 of Preliminary Materials for DEP) did not report these effects at the lowest dose tested. EPA is seeking public discussion on the significance of the low-dose effects, given this potential inconsistency within the DEP database but similarity with other phthalates.
- Science issue 2. There are some studies, in both humans and experimental animals, which indicate that the female reproductive system may also be a target for DEP-induced toxicity. Specifically, altered fertility and birth outcomes have been reported (see Table A-10 on page A-42 of Preliminary Materials for DEP). EPA is seeking public discussion on the significance of these effects, given this potential inconsistency with other phthalates.
Hexabromocyclododecane (HBCD): Kathleen Newhouse & April Luke, Assessment Managers
Key Science issues:
- Science issue 1. Changes in thyroid hormone levels have been reported following HBCD exposure in several rodent toxicity studies (see Table A‑2 on page A-6 of Preliminary Materials for HBCD). The assessment will consider biological significance of these changes. EPA is seeking public discussion on the levels of change in thyroid hormones that are biologically significant.
- Science issue 2. The preliminary materials summarize evidence on possible liver and thyroid effects (see Sections A.2.1 and A.2.2) and list mechanistic studies that may relate to these effects (see Table B-1 on pages B-2 through B-11). A potential relationship between the liver and thyroid effects as a result of HBCD exposure has been proposed in the literature. EPA is seeking public discussion on what sequence(s) of mechanistic events may be hypothesized to link effects in the liver and the thyroid.
- Science issue 3. After the epidemiological and experimental studies on each health effect have been synthesized, mechanistic information will be reviewed and synthesized to evaluate potential modes of action (MOAs) and/or adverse outcome pathways (AOPs). Because mechanistic studies are numerous and their designs are highly heterogeneous, extracting these data in tabular form before identifying the health effects and MOAs/AOPs that are scientifically plausible would be a resource intensive, yet potentially uninformative effort. Instead, the preliminary materials provide a summary table of mechanistic studies including general information on the test systems and assays used, the parameters that were measured, and the possible health effects to which each mechanistic study may relate (see Table B-1 of Preliminary Materials for HBCD). We believe this information provides an opportunity for scientific discussion of the level of support for possible MOAs/AOPs. EPA is seeking public discussion about (1) MOAs/AOPs that might be supported by the studies cited in Table B-1 and (2) suggestions for improving the presentation of this type of information at this early stage of draft development.
General Comments:
