Meeting Objective:
The objective of this meeting was to obtain input from the scientific community and the public on studies and data that will be used in the assessments that are under development. Specifically, EPA was seeking input on key science questions identified for discussion and preliminary materials including draft literature searches and associated search strategies, the approach for selecting primary studies to be included in the evidence tables, the approach for evaluating methodological features of studies, evidence tables, and exposure-response arrays.
In October 2014, EPA’s IRIS Program announced an agreement with the National Academies’ National Research Council (NRC) to arrange for independent experts to attend the IRIS bimonthly public meetings, in order to provide input on the science underlying the development of IRIS assessments through participation in IRIS Bimonthly Public Science Meetings. These independent experts, speaking on their own behalf, attended the February meeting to contribute to the scientific discussions of issues amongst EPA, stakeholders, and the public. This meeting was the first meeting where NRC identified experts were invited to join the public discussion on key science questions and preliminary assessment materials. The agenda specifies the discussants that were identified by NRC.
Dates:
The meeting was held on February 25-26, 2015 from 9:00am - 5:00pm 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.
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Meeting Agenda
February 25-26, 2015, 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: Agenda February 25-26, 2015 Public Meeting (PDF) (3 pp, 105 K, About PDF)
Preliminary Materials:
Butyl Benzyl Phthalate (BBP): Xabier Arzuaga & Andrew Hotchkiss, Assessment Managers
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Diisobutyl Phthalate (DIBP): Erin Yost & Todd Blessinger, Assessment Managers
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Dibutyl Phthalate (DBP): Susan Makris & Andre Weaver, Assessment Managers
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Key Science Questions:
Science Question 1. Emerging areas of phthalate research.
- Much of the research with respect to phthalates has focused on male reproductive effects after exposure in utero (e.g., "phthalate syndrome" in rats or "testicular dysgenesis syndrome" in humans). There are emerging areas of research focusing on other outcomes, however, including allergy and asthma, and neurodevelopmental and metabolic health effects. EPA is seeking public comment on these new areas of research, particularly pertaining to relationships among endpoints and underlying mechanisms to consider in its evaluation of this literature.
- BBP: see Evidence Tables 3-9 through 3-16
- DIBP: see Evidence Tables 3-9 through 3-15
- DBP: see Evidence Tables 3-5 through 3-7, 3-9 through 3-16, and 3-33 through 3-35
- Experimental and epidemiological studies have reported an association between phthalate exposure and adverse pregnancy outcomes (specifically, preterm birth, pregnancy loss). Few studies have addressed the potential mechanisms related to these effects. However, human, experimental animal, and in-vitro studies have reported alterations in the production and/or levels of progesterone, reactive oxygen species (ROS), or prostaglandins following exposure to phthalates (Ferguson et al., 2014; Tetz et al., 2013). EPA is seeking public discussion on the available epidemiological and experimental data on phthalate exposure and effects on pregnancy outcomes and female reproduction and the potential mechanisms associated with these effects.
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Science Question 2. Considering phthalate syndrome effects as a single outcome. The 2008 National Research Council report on cumulative risk of phthalates (NRC, 2008) included the following effects as part of the phthalate syndrome: retention of nipples and/or areolae, reduced anogenital distance, and a number of malformations of the male reproductive tract including underdeveloped or absent reproductive organs, undescended testes (cryptorchidism), malformed external genitalia (e.g., hypospadias), decreased sperm production and infertility, reduced Leydig cell function, and increased incidence of gubernacular malformations. EPA has presented the data on phthalate syndrome effects as separate, individual outcomes in the phthalate animal evidence tables and is considering evaluating these effects together, as a single outcome, during the assessment development. EPA is seeking public discussion on this approach.
BBP: see Evidence Tables 3-18 through 3-21
DIBP: see Evidence Table 3-18
DBP: see Evidence Tables 3-18 through 3-25
- Presentations
Facilitated discussion of science issue with all attendees, including:
- Kim Boekelheide*, Brown University School of Medicine (PDF) (2 pp, 559 K, About PDF)
- Rebecca Clewell, The Hamner Institutes for Health Sciences, on behalf of Valerus Specialty Chemicals (PDF) (4 pp, 218 K, About PDF)
- Pam Factor-Litvak*, Columbia University Mailman School of Public Health
- Paul Foster, NIH/ National Institute of Environmental Health Sciences(NIEHS)/National Toxicology Program (NTP) (via telephone)
- Earl Gray, EPA/National Health and Environmental Effects Research Laboratory (NHEERL) (via telephone)
- Russ Hauser*, Harvard University T.H. Chan School of Public Health
- Sheela Sathyanarayana*, University of Washington School of Medicine (via telephone)
Science Question 3: Biologically relevant level of change in testosterone concentration. Decreased testosterone levels have been reported following phthalate exposure in several rodent toxicity studies. However, there are insufficient data to determine the biologically relevant decrease in fetal testicular testosterone in rats; i.e., information linking testicular testosterone alterations to downstream in vivo toxicology outcomes (e.g. reproductive tract malformations). EPA is seeking public input on the level of change in testosterone concentration considered to be biologically relevant.
BBP: see Evidence Table 3-19
DIBP: see Evidence Table 3-18
DBP: Evidence Tables 3-23
- Presentations
Facilitated discussion of science issue with all attendees, including:
- Kim Boekelheide*, Brown University School of Medicine (PDF) (2 pp, 189 K, About PDF)
- John Butala, Toxicology Consultants, Inc., on behalf of Valerus Specialty Chemicals (PDF) (4 pp, 112 K, About PDF)
- Rebecca Clewell, The Hamner Institutes for Health Sciences, on behalf of Valerus Specialty Chemicals (PDF) (4 pp, 355 K, About PDF)
- Earl Gray, EPA/National Health and Environmental Effects Research Laboratory (NHEERL) (via telephone)
- Richard Ivell*, University of Nottingham School of Biosciences (via telephone)
- Kamin Johnson, The Dow Chemical Company (via telephone)
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Science Question 4: Use of phthalate mechanistic data. There are mechanistic data (including studies from different species and strains of test animals and human in vitro and xenograft tissue culture preparations) associated with male reproductive developmental effects after gestational exposure to phthalates. There are also other mechanistic data for phthalates that may be associated with one or more health outcomes. EPA is seeking public discussion on the concordance across studies and species and applicability to humans of in-vivo, in-vitro, and xenograph studies, and how mechanistic data for phthalates can inform the hazard identification and dose-response analysis for each hazard.
- Presentations
Facilitated discussion of science issue with all attendees, including:
- Kim Boekelheide*, Brown University School of Medicine (PDF) (2 pp, 227 K, About PDF)
- Rebecca Clewell, The Hamner Institutes for Health Sciences, on behalf of Valerus Specialty Chemicals (PDF) (5 pp, 354 K, About PDF)
- Paul Foster, NIH/National Institute of Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP) (via telephone)
- Earl Gray, EPA/National Health and Environmental Effects Research Laboratory (NHEERL) (via telephone)
- Kamin Johnson, The Dow Chemical Company (via telephone)
- Sheela Sathyanarayana*, University of Washington School of Medicine (via telephone)
Science Question 5: Relevance of non-androgen related male reproductive effects. Evidence suggests that phthalate-induced alterations in the development of the male reproductive system may be mediated through both androgen dependent and independent pathways. EPA is seeking public discussion on the effects that are not related to disruption in androgen production and levels, including alterations in insl3 levels, and fetal/postnatal germ cell effects and the relevance of these effects to human health.
BBP: See Evidence Table 3-20
DIBP: See Evidence Table 3-18
DBP: See Evidence Tables 3-20 and 3-25
- Presentations
Facilitated discussion of science issue with all attendees, including:
- Kim Boekelheide*, Brown University School of Medicine (PDF) (2 pp, 137 K, About PDF)
- Rebecca Clewell, The Hamner Institutes for Health Sciences, on behalf of Valerus Specialty Chemicals (PDF) (3 pp, 378 K, About PDF)
- Paul Foster, NIH/National Institute of Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP) (via telephone)
- Earl Gray, EPA/National Health and Environmental Effects Research Laboratory (NHEERL) (via telephone)
- Richard Ivell*, University of Nottingham School of Biosciences (via telephone)
- Kamin Johnson, The Dow Chemical Company (via telephone)
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References:
- Ferguson, K; Cantonwine, D; Rivera-González, L; et al. (2014) Urinary phthalate metabolite associations with biomarkers of inflammation and oxidative stress across pregnancy in Puerto Rico. Environ Sci Technol 48: 7018-25.
- Tetz, L; Cheng, A; Korte, C; et al. (2013) Mono-2-ethylhexyl phthalate induces oxidative stress responses in human placental cells in vitro. Toxicol Appl Pharmacol 268: 47-54.
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