April 11, 2018
Toxics Use Reduction Institute Science Advisory Board Meeting Minutes
Draft for Board Review
April 11, 2018
Massachusetts Department of Environmental Protection – 2nd Floor, 1 Winter Street, Boston
12 PM
Members present: David Williams (Chair), Christy Foran, Robin Dodson, Chris Rioux, Hilary Hackbart, Wendy Heiger-Bernays, Amy Cannon, Denise Kmetzo, Ken Weinberg, Margo Newman
Members not present: Larry Boise (Vice-Chair)
Program staff present: Liz Harriman (TURI), Heather Tenney (TURI), John Raschko (OTA), Tsedash Zewdie (MassDEP), Mary Butow (TURI), Rich Bizzozero (OTA), Jenny Outman (MassDEP/OGC)
Others present: Katherine Robertson (MCTA), Steve Korzeniowski (FluoroCouncil), Ruthann Rudel (Silent Spring Institute), Natalie Banacos (Boston University School of Public Health), Andy Irwin (Irwin Engineers), Jianguo Liu (Visiting Scholar – Boston University), Robert Rio (Associated Industries of Massachusetts), Margaret Gorman (ACC), Renee Lani (FluoroCouncil), Erin DeSantis(ACC), Bill Coyne (Coyne Legislative Services for ACC), Phil Goodrum (Fluorocouncil)
Welcome and Introductions
Program Updates
- A TURA Program Update was circulated that had also been handed out at the recent Advisory Committee Meeting. (available at: https://www.mass.gov/event/april-4-2018-meeting-of-the-advisory-committee-to-the-administrative-council-on-toxics-use)
- TURA Continuing Education Conference – April 25, 2018 – Keynote speaker: Dr. Laura Vandenberg.
- TURI has moved offices and laboratory to Boott Mills in Lowell.
- Any other companies in MA interested in filling out the Nanomaterials survey may still do so.
- The Administrative Council voted to List C1-C4 Halogenated hydrocarbons/halocarbons not otherwise listed. Will begin 30A regulatory process including opportunity for public comment.
Approve January Meeting Minutes
Minutes were approved as written; 7 in favor, 2 abstentions.
Completion of PFAS Discussion and Vote:
The Program described the distribution of information. At the previous meeting, the board had listed endpoints and effects of concern for each of the substances to facilitate a final review and vote. This List of Concerns referencing relevant studies was distributed to the Board and Stakeholders in between the meetings and comments received on those were distributed to all parties. At this meeting, the Board took up discussion of each of the 4 chemicals individually. Working from the previous List of Concerns and cited studies they identified their primary concerns with the substances from an environmental, health and safety perspective.
PFHxS
The List of Concerns for PFHxS was written on the White Board and members were invited to identify endpoints of greatest concern and the most relevant studies supporting these.
PFHxS Concerns (from White Board):
(*)Persistence – not expected to degrade under environmental conditions (see EHS summary)
(*) Thyroid Effects – epidemiological study total T4 increased for female > male; potential interaction TTR; NTP significantly alter thyroid hormone
(*)Liver/metabolic Effects – Das ’17 (increased liver weight, triglycerides, steatosis in mice), Wolf ’08, Butenhoff ‘09
○ Endocrine Effects – Will there be (from long term exposure)? Das ‘17
* Neurodevelopmental effects – Viberg ’13 PND alter cognitive function male + female; dose response related; irreversible; Lee + Vi ’13 alter neuroprotein levels Lyall ’18 no assoc., Zhang ’18 reading skills no assoc.; Mechanisticà 4 studies with no assoc. (other PFAS showed assoc) ’10 Hoffman(highest quartile ↑ADHD)
* Corrosivity – highly corrosive
○ Bioaccumulation – tricky; vBvP ECHA; Houde ’06; Some evidence
** Presence in Serum/Environment 8.5 yr Cord blood, breast milk Glynn ↑concentration over time
Neurotoxicity
Asthma
○ Mobility
A visitor noted a document from Norway citing a lot of bioaccumulation.
The representative from DEP noted an NTP study which came out the prior day and noted significant alteration of thyroid hormone in every PFAS studied except PFBA.
Motion: SAB Recommends listing PFHxS on the TURA list because of persistence, bioaccumulation, mobility, corrosivity and mammalian toxicity: thyroid, liver/metabolic, and endocrine effects. 8 in favor, 2 abstaining. One Board member noted their abstention due to uncertainty around the bioaccumulation and liver/metabolic effects; the other Board member noted their abstention due to this being their first meeting.
Vote to revise motion to “PFHxS and its salts,” moved and seconded: 8 in favor, 2 abstaining.
PFHxA
The List of Concerns for PFHxA was written on the White Board and members were invited to identify endpoints of greatest concern and the most relevant studies supporting these.
PFHxA Concerns (from White Board):
* Persistence – very high - (Danish EPA, Also not removed by WWT)
* Mobility – very – Zhao, Cai 2012 (Antarctic snow)
* Thyroid Effects – Ren’ 16 TTR Human does bind weakly, Epi Study Anti Thyroid immune response Li ’17 wt. change Thyroid increased in female rat; NTP
Liver Effects – Loveless ‘09 + Chengelis
Endocrine Effects
* Developmental effects – GS moderate à Loveless (pup wt.), Iwai ’14 (ammonium salt; same as Charles River) à stillborn pups (Iwai redo). Also reduced postnatal survival.
Was internal dose measured? serum concentration? blood level lower, plasma, similar effects
* Corrosivity – pKa -.16 est.
* Presence in Serum/Environment/Toxicokinetics – (blood protein binding) Rat <1hr; human 32 days (visitor noted result was not from half-life study and so unknown). constant dose
Neurotoxicity
* Kidney Effects – Klaunig ’15, Chengelis ‘09
Bioaccumulation – human breastmilk 70%; Kang 2016
Ecotoxicity
Discussion noted that PFHxA is very mobile - potential global transport (Zhao 2012).
For thyroid effects, PFHxA binds to human TTR circulating protein (weakly). The new NTP report notes significant alteration of thyroid hormone as well. Loveless 2009 shows thyroid weight changes in female rodents at the highest dose. It is difficult to tease apart potential effects on liver. PPARα binding occurs in the liver – the liver outcome may be manifesting elsewhere in the body. The epidemiological study Li et al 2017c showed serum levels associated with thyroid globulin antibodies but no difference in TSH, T4, T3. A visitor commented that it may be an adaptive response, rather than adverse.
For developmental effects it was noted that Charles River is the same as Iwai & Hoberman. A visitor noted that results seen in Iwai & Hoberman were similar to those seen in historic controls. It was questioned whether internal dose or serum concentration was measured.It was noted that stillborns should not be viewed as the significant endpoint. There is a suggestion of developmental effect which could be even greater in humans.
As a strong acid PFHxA is very corrosive. In concentrated form it is an acute occupational hazard, however, a representative from ACC noted it is not in commerce.
The toxicokinetics of PFHxA has been brought up at multiple meetings. The rat half-life is less than 1 hour and the human half-life is estimated at 32 days. A visitor noted that the study estimating 32 days wasn’t designed as a half-life study. It was noted that the dosing to humans may be constant.
For bioaccumulation the human breast milk concentration is the highest reported to date of short chain and compared to PFOS (Kang 2013).
A visitor commented that the residence time in blood may be very short and not show effects. The French ANSES Toxicity Reference Value is less than 1 mg/kg/day. The science is developing rapidly and PFAS are really hard to clean up once they are out there.
It was highlighted that PFHxA is extremely persistent and there is no way to easily clean it up. A visitor noted that the Emerging Contaminants Summit identified the ability to remove short chains from groundwater using ion exchange resins (granulated carbon doesn’t work well for short chain compounds).
Motion: SAB recommends listing PFHxA and its salts on TURA list due to strong evidence on persistence, mobility, corrosivity, and mammalian toxicity: thyroid and liver, with concerns for kidney and developmental effects.
9 in favor, 1 abstaining. The member abstaining noted their abstention due to this being their first meeting.
PFBS
The List of Concerns for PFBS was written on the White Board and members were invited to identify endpoints of greatest concern and the most relevant studies supporting this.
PFBS Concerns (from White Board):
Asthma
Immunotoxicity - Corsini
* Persistence
* Mobility – Zhao 2012 & Danish EPA
* Thyroid – Feng T4, T3; new NTP
Endocrine – Gorrochategui ↓aromatase, additivity? Human placental cell line
◦ Hematological - Leider
* Developmental – Feng ’17 ↓ weight offspring, estrogen, progesterone, T3+
* Corrosivity – -3.31 est. pKa
Bioaccumulation
Presence in Environment
◦ Neurotoxicity – Slotkin ’08
Kidney
◦ Reproductive toxicity – Wang ’17 Increased female infertility
Feng 2017 showed that PFBS was related to a decrease in weight, T4/T3↓ for offspring (Lieder 2009b).
Effects on Estrogen/progesterone was also noted.
Motion: SAB Recommends listing PFBS and its salts on TURA list due to persistence, mobility, corrosivity and mammalian toxicity: thyroid and developmental toxicity, with additional concerns for reproductive toxicity, neurotoxicity and immunotoxicity.
9 in favor, 1 abstaining. The member abstaining noted their abstention due to this being their first meeting.
PFBA
The List of Concerns for PFBA was written on the White Board and members were invited to identify endpoints of greatest concern and the most relevant studies supporting this.
PFBA Concerns (from White Board):
* Persistence
* Mobility
* Thyroid – Bjork and Wallace ‘09
* Liver/Endocrine Effects – Wolf ’08, Foreman ’09 PPARα Rosenmai PPAR α + γ downstream genes spermatogenesis, cholesterol
* Hematological – Butenhoff ’12
* Developmental – Das maternal liver weight ↑ (reversible), ↑full litter resorption, delayed eye opening
* Corrosivity – pH = 1
Phytoaccumulation – Fluorocouncil Report, Scher ‘18
Presence in serum
Presence in environment
Wolf 2008 shows much stronger activation in the mouse PPARαcompared to human. Liver hypertrophy was shown but there was no evidence of cell damage (hepatocytes). EPA might classify this as an adaptive response.
Das 2008 showed delayed puberty.
Butenhoff showed an increase in thyroid weight in females and a decrease in circulating T4. A visitor noted that the authors were concerned about the analytical method and that ANSES had similar conclusions. In vitro and cell studies looked at human and rodent hepatocytes. Weiss 2009 didn’t show that there would be competition for binding. A visitor noted that in Ren, [TTR competitive] binding [assay], relative potency was less than PFOA and that in the Li epidemiological study, there was not an association with changes in circulating thyroid hormones. Butenhoff also showed hematological effects.
Motion: SAB Recommends listing PFBA and its salts on TURA list due to persistence, mobility, corrosivity and mammalian toxicity: liver/endocrine, with additional concerns for thyroid, developmental toxicity, hematological effects, and phytoaccumulation.
9 in favor, 1 abstaining. The member abstaining noted their abstention due to this being their first meeting.
PFAS: Precursors and range of substances
Discussion tabled until next meeting.
Next Meeting
Meeting date to be determined.
Handouts
Draft EHS Summary for PFHxS
Draft EHS Summary for PFHxA
Draft EHS Summary for PFBS
Draft EHS Summary for PFBA