June 26, 2014
Toxics Use Reduction Institute Science Advisory Board Meeting Minutes
June 26, 2014
Saltonstall Building, 9th Floor, OTA Conference Room
12:30 PM
Members present: Dave Williams (Chair), Martha Mittelstaedt, Larry Boise (Vice-Chair), Christine Rioux, Robin Dodson, Kenneth Weinberg
Others present: Mary Butow (TURI), Liz Harriman (TURI), Heather Tenney (TURI), Rick Reibstein (OTA), Colin North (ExxonMobil Biomedical Science), Trisha McCarthy (ACC), Steve Rosario (ACC), Susan Peck (DEP), Sahar Osman-Sypher (ACC), Lisa Marie Nespoli (Bayer MaterialScience LLC), David Kiddoo (AlphaGary MexiChem)
Members not present: Hilary Hackbart, Igor Linkov, Amy Cannon
Welcome and Introductions
Program Updates
• The More Hazardous List prioritization process (which included 4 substances that are priorities for both the SAB and the Advisory Committee), was reviewed at the most recent Administrative Council meeting. The Council was very engaged and had many questions and comments. They are concerned about regrettable substitutions and would like to know more about how they can prevent this from happening.
• The draft Policy Analysis for Hydrofluoric Acid (HF) is available and will be circulated to the Board.
• Program staff also gave an update on a question from the May meeting regarding PCBs and PBBs. PCBs are on the TRI and TURA lists, and are U.S. EPA PBTs (Persistent, Bioaccumulative and Toxic) and therefore are automatically designated as Higher Hazard Substance (HHS) with the EPA threshold of 10 lbs. These are also on the More Hazardous list. PBBs are on the TRI and TURA list but are not U.S. EPA PBTs, not HHS, and are not on the More Hazardous list.
Approve May Meeting Minutes
Vote: Approved: 5 in favor, 1 abstention.
CERCLA Categories: Phthalate esters
Several items were addressed in the document since the last meeting including: re-organization of selected phthalate esters by carbon chain length; addition of structures; tables moved to appendix; follow up on some questions; notes on outstanding questions, e.g. low-dose, cumulative effects, summary findings; addition of a glossary. Comments on the document were received from ACC and BASF.
Cumulative Effects Discussion.
The Board would like to add tables for the key studies. There was a comment about how mixtures in some studies include phthalates and other substances.
Most studies look at anti-androgenic substances. Dr. North drew a diagram showing the impact of anti-androgenic phthalates: progression begins with disruption of an enzyme which inhibits testosterone synthesis -> decreased testosterone production -> decreased Androgen receptor activation -> hypospadias. He noted these effects (hypospadias are common in the C4-C6 range).
Board members had several comments/concerns:
• Which data support that certain phthalates decrease testosterone, or interrupt synthesis?
• Some studies have shown cumulative effects for certain phthalates. Does the weight of evidence support cumulative effects for the high molecular weight phthalates, if the overwhelming effects were from the transitional phthalates (Benson, Kortenkamp/Faust- see HQ/HI discussion)?
• Concerns with enzyme synthesis interference, could have broader implications, i.e. downstream effects. Caution that this could lead to cumulative effects.
• Focus has been in area of androgens.
• All the cumulative effects studies include some of the C4-C6; can say there is concern, but don’t have good data across higher molecular weight phthalates. Mixtures in these studies contain many of those already on the TURA list.
• For low molecular weight phthalates, some have atypical metabolites, so the health effects of most concern for them might not be cumulative with other phthalates. E.g., DMEP, oxidizing methoxy group to become ether is a different mechanism of toxicity. DAP also doesn’t have typical phthalate metabolites. Functional groups within them are very different than typical side chains. Are there other C1-C3 phthalates that have more typical metabolites? E.g., Dipropyl phthalate?
• Need to include negative effects as well (both single studies and mixtures).
• Do we have evidence of anti-androgenic effects for high molecular weight phthalates other than DINP?
Draft summary statements:
• Some studies have shown cumulative effects from different phthalate esters (cite studies). There are many data gaps, particularly for high molecular weight (HMW) phthalate esters.
• Most studies include transitional (C4-C6) phthalate esters, and so cumulative effects of less potent HMW may not be evident.
• Some phthalate esters may act differently (DAP, DMEP), and those health effects are not expected to be cumulative
• Concerns with anti-androgenic phthalate esters that interfere with enzymes and reduce testosterone synthesis include not only the anti-androgenic effects, but also other impacts from enzyme interference.
Next steps:
• Add table of studies
• Someone from DTDP group review Saillenfait in detail
Low-Dose Effects Discussion.
The Board discussed the definition of “low-dose”. A table will be added for the low-dose effects that includes both the original dose, and the “converted dose”. EM-BMS to send guidance for converting dietary concentrations. The ECHA comments on thyroid effects from Wenzel, 2005 will be reviewed.
Carbon Chain Length Table.
Table was reviewed and edits were suggested. Program will include a key and title for the final version which will be included in the Summary document.
Meta- and Para- phthalate esters.
EMBMS noted that this same issue with regard to toxicological activity due to functional chemistries applies to the side chains for this group as well. (e.g. DAP/DMEP see above).
The Board requested a literature search be performed for all information on these selected meta and para PEs. They specifically requested additional information on: reactivity, DEHT, pentyl iso-pentyl [ECHA, SVHC], dimethyl isophthalate, terephthalic acid metabolites. A correction was noted and will be confirmed for 84777-06-0, as it is likely an ortho.
Tabled discussion: Review of ACC comments and any changes to the document based on the comments; Summary section comments.
Diisocyanates Category: Review of Component Substance Data
The EPA TRI and TURA Diisocyanates category is being reviewed to determine if the entire category should be on the SAB’s More Hazardous Chemicals list. Currently MDI and TDI are on the MHC list, but MDI is now reported as part of the larger Diisocyanates category. TDI is still reported separately under 3 individual CAS numbers.
A screening EHS table of health and environmental endpoints was reviewed for the 20 individual substances that comprise the Diisocyanates category. Discussion focused on chemicals and chemical structures that are part of the category. The category includes both aliphatic and aromatic substances. There was discussion about whether it would be helpful to consider aliphatic and aromatic substances separately. Bayer MS on behalf of ACC would like to submit comments about the categorization of the chemicals.
Program noted that they spoke with an expert on diisocyanates, Dr. Dhimiter Bello. He is willing to provide input or share his expertise with the board if that would be helpful.
Next steps:
• Add EPA federal register document
• Look at both chronic and acute pulmonary effects, particularly sensitization
• Access and review REACH data on the 7 isocyanates for which it is available
• Confirm: does dermal exposure lead to respiratory sensitization?
Motion to Adjourn.
Next Meeting
Wednesday, September 17th, 12:30PM (tentative)
Handouts (limited copies available):
• TURI – Phthalate Ester Summary Document draft – Version 2
• TURI – 10 Selected Phthalate Esters - Carbon Chain Length by Health Effect Table
• TURI – Phthalate Ester EHS Summary for selected Meta- and Para- substances (Excel Sheet)
• TURI – Glossary for Phthalate Ester Summary Document
• TURI – Isocyanates Scientific Data (Excel Sheet)
• ACC – Comments for Use by Massachusetts TURA SAB Regarding Phthalates
• BSF – Comments on DPHP
• EPA – 1997 Isocyanate Chemical Category Document
• Rider 2010 – Cumulative Effects of In Utero Administration of Mixtures of Reproductive Toxicants that Disrupt Common Target Tissues via Diverse Mechanisms of Toxicity
• Wenzel 2005 – Modulation of iodide uptake by dialkyl phthalate plasticisers in FRTL-5 rat thyroid follicular cells