March 27, 2019
Toxics Use Reduction Institute Science Advisory Board Meeting Minutes
March 27th, 2019
DEP, 1 Winter Street, Boston
12:30 PM
Members present: Robin Dodson (Vice-chair), Hilary Hackbart, Wendy Heiger-Bernays, Denise Kmetzo, Margo Newman, Heather Lynch, Chris Rioux, Christy Foran
Members not present: Dave Williams, Amy Cannon, Ken Weinberg
Program staff present: Liz Harriman (TURI), Heather Tenney (TURI), John Raschko (OTA), Lindsey Pollard (TURI)
Others present: Katherine Robertson (MCTA), Erin DeSantis(ACC), Renee Lani (Fluorocouncil), Steve Korziniowski (Fluorocouncil), Bill Coyne (Coyne PC for ACC), Carol Holahan (Foley Hoag ACC)
Welcome and Introductions
Program Updates
- Printed handout of program activity (circulate)
- TURI open EHS and Learning Support Specialist positions
- Upcoming TUR Planner Continuing Education Conference 4/4
- TURI new Co-Directors announcement (circulate)
- TURA Program FY18 Annual Report to the Governor
- Artificial Turf and Playground Surfacing reports and factsheet
- C1-C4 Halogenated Hydrocarbons category reportable for calendar year 2019
- Flame Retardants in Gyms (fact sheet)
- PFAS updates:
Senate Bill PFAS as Hazardous Substances under 302 CERCLA
Fluorocouncil and IC2 Webinar end of January; Questions and Answers and Webinar posted on LibGuide.
Cost of Inaction report, Nordic Council of Ministers
Minutes
The minutes from the last meeting were reviewed and there was a vote to approve: 7 in favor, 1 abstained. It was explained that you can still vote to approve minutes even if you were not at that meeting.
Heather reviewed the Board’s work on PFAS to date. We began with PFOA and PFOS over two years ago, then reviewed 4 shorter chain PFAS, then PFHpA and PFNA. All were recommended for listing. Common effects were extreme persistence, mobility in the environment, liver/metabolic effects, thyroid, and corrosivity of the concentrated acid. Additional concerns included bioaccumulation and phytoaccumulation, endocrine effects, kidney, immune system and developmental/reproductive effects, among others.
GenX
GenX was introduced at the last meeting where we looked at the big picture for GenX using primarily the EPA Draft Toxicity Assessment. Members then chose focus endpoints to dig deeper.
Concerns were documented on the White Board as follows:
*Persistence: Yes. No biodegradation, hydrolysis or photolysis observed, only thermal degradation possible (ECHA 2019) [Van Hoven & Nixon 2008, Kawashima 2009, Lili 2010]
Bioaccumulation: fairly low, limited info. some evidence of phytoaccumulation, [Expertisecentrum PFAS 2018] and [Van Bentum 2017]
*Mobility: Transport – drinking water NC, not removed by standard WT; GAC has limited efficiency, Maybe IE? (Hopkins 2018); transport via groundwater& atmospheric; low sorption to soil (Pan 2018) “Ubiquitous across global environment”
Toxicokinetics: binds to proteins; absorbed and distributed to liver/plasma. Excreted in urine not metabolized; species and sex differences in ½ life (animal: mice & rat – Gannon 2008); human ½ life unknown (ECHA 2018 assumed to be one to many days); dermal absorption possible
*Liver: differences in results in two DuPont studies. Cell necrosis- single cell vs. multi. Adverse vs. Adaptive. 90 day no inflammation; hepatocellular hypertrophy; AST, ALT, ALK phosphate blood parameters; Sheng uptake liver cells hL-FABP; Wang ↑ increase liver weight, LDL cholesterol ↑, ↑ALT, ↓bilirubin; different animals, different studies; study design mechanistic pathway, PPARa humans not carcinogenic, mediated response in humans happens and is defensible; liver tumors.
Dev/Repro: DuPont 2010 doesn’t appear to be selective DRT; higher doses than maternal toxicity, extra rib; also observed maternal liver and kidney effects in this study. 1/3 failed to deliver; missing uteri; [mice 5 mg/kg/day] early delivery may be secondary; Conley 2019 new EHP pub - higher maternal liver weight, ↓serum thyroid and lipid maternal, ↑ PPAR maternal and fetal.
Immunotox: Rushing 2017 ↑T cells both sexes, ↓ TDAR female, ↓significant globulin levels, ↑ spleen wt. DuPont 2006, 2007 equivocal results for local lymph node assay; USFDA 2002 globulin levels assoc w antibody production
Cancer: (Rae 2015) DuPont highest dose liver tumors females; 50 mg/kg/day pancreas; high mortality in control, low and mid dose did not contribute to tumor.
*Corrosivity: Corrosive pKa compared to PFOA; permanent eye damage, reversible skin damage (Carpenter 2007 from ECHA 2019); Companies report severe skin burns
Kidney: DuPont 2010 p.45 ↑kidney weight; EPA significant difference in kidney weight, ↑BUN (DuPont 24447-2008, 2009); 2013 relative kidney weight not affected - male rat)
For persistence additional notes show that thermal degradation occurs at high temperatures. It was noted that in terms of bioaccumulation there is human exposure from food and fish but it is unclear how large a contribution they make. GenX was noted to be mobile in water and found in areas distant from known sources. Water treatment to remove GenX was discussed briefly; GAC (granulated activated carbon) has limited efficiency, ion exchange may be effective, but there are operational challenges.
For toxicokinetics information pertained to an oral route. Gannon (2016) gave animal half-lives of hours to days. Uncertainty around using animals to predict human half-lives was noted; ECHA says in animals it varies between one and several days, and in humans it is expected to be considerably higher.
There was extensive discussion of liver effects. It was unclear whether some study results were adaptive or adverse. There were also questions about cell necrosis and whether it was single cell versus multi cell. There were differences in effects shown in the two main DuPont studies. Wang and Sheng studies look at liver cells and binding to liver fatty acid binding proteins (FABP) as a way to get them into cells. Wang shows absolute and relative liver weights, association with increased LDL cholesterol, decreased total bilirubin, increased ALT, and other liver effects. These studies look at mechanistic pathways and see what is happening. So even though PPARa is often dismissed for humans, even though carcinogenic effects may not relate to humans, there are still effects on the liver. There are liver tumors in animals as well.
There do not appear to be selective developmental effects - effects seem to be secondary to maternal toxicity and liver effects. The extra cervical rib may or may not be important. Vaginal patency may be secondary to body weight loss. There were many secondary effects, including liver and kidney effects. Early delivery and increased liver weights were noted that might be secondary. Concerns about the mouse study were noted, 11 pairs failed to deliver and many missing uteruses (both in controls and in dosed group) reduces the power of the study – however it was noted that EPA still used this study. Developmental effects NOAEL (F1) 0.5 mg/kg/day; LOAEL (F1) = 5 mg/kg/day. Conley 2019 (just getting published in EHP) showed higher maternal liver weight, lower serum and thyroid weight, and upregulated serum pathways.
For immunotoxicity the one main study (Rushing 2017) showed increasing T cells, decreasing TDAR and globulin levels and increased spleen weight. Alterations in the serum levels of globulin can be associated with decreases in antibody production (USFDA 2002). DuPont 2006, 2007 showed equivocal results for lymph node assay; decreases in serum globulin levels. It was noted that several studies saw changes in globulin levels and also that there were some sex differences.
For the cancer endpoint, the DuPont 2013 rat study (Rae 2015) showed a statistically significant increase in liver tumors in females at the highest dose (500 mg/kg/day for 2 years) and pancreas in males at the highest dose (50 mg/kg/day). It was noted that there were other significant effects and that there was a marked decreased survival rate across all groups including the control.
Companies self-classification under CLP report severe skin burns.
A representative from the Fluorocouncil asked why we are discussing a chemical not made or used here. It was also inquired as to whether similar substances from other manufacturers would be discussed.
Discussion followed regarding what effects would justify listing and the Board’s confidence level in existing data. The Board starred persistence, mobility and corrosivity as key effects and starred liver effects after extensive discussion. It was discussed whether there was sufficient evidence for liver toxicity. It was noted that liver effects were seen in studies that were not studying the liver, as well as studies that were. Supporting mechanistic studies and the fact that consistency is seen across different study durations improved confidence levels. It was also noted, for example, that Sheng looked at the body of literature and identified GenX as a liver toxicant. Effects on the kidney and concerns regarding immunotoxicity were noted as well.
Motion: SAB recommends listing HFPO-DA and its ammonium salt on the TURA list due to persistence, mobility, corrosivity, and liver toxicity. Second. 7 in favor, 1 opposed.
The other GenX related substances such as those ECHA included will be discussed next time.
Phosphonic/phosphinic acids
The EHS Summary for the phosphonic and phosphinic acids (PFPA and PFPiA) was distributed. The low LD50 was noted. There is not much information about these substances – supporting articles are on the LibGuide (Wang and DaSilva). The Fluorocouncil does not have information to offer on these. We will discuss PFPA and PFPiA further at the next meeting.
Range of Perfluorinated Substances
As the board delves into the universe of substances and breakdown chains, there is interest in hearing from additional experts.
Next Meeting
May 8 or 9th for next meeting
Handouts:
-Updated EHS Summary PFPA and PFPIA for the MA TURA Science Advisory Board Meeting – March 27,2019
-Human Health Toxicity Values for Hexafluoropropylene Oxide (HFPO) Dimer Acid and Its Ammonium Salt (CASRN 13252-13-6 and CASRN 62037-80-3) Public Comment Draft (EPA 2018), summary pages
-An Oral (Gavage) Reproduction/Developmental Toxicity Screening Study of H-28548 in Mice (DuPont 2010), summary pages