May 31, 2017
Toxics Use Reduction Institute Science Advisory Board Meeting Minutes
May 31, 2017
Massachusetts Department of Environmental Protection – 2nd Floor, 1 Winter Street, Boston
12:30 PM
Members present: David Williams (Chair), Larry Boise (Vice-Chair), Denise Kmetzo, Christy Foran, Ken Weinberg, Robin Dodson
Members not present: Amy Cannon, Chris Rioux, Hilary Hackbart
Program staff present: Liz Harriman (TURI), Heather Tenney (TURI), John Raschko (OTA), Tsedash Zewdie (DEP), Mary Butow (TURI)
Others present: Patricia McCarthy (Coyne Legislative Services for ACC), Katherine Robertson (MCTA), Margaret Gorman (ACC), Jessica Bowman (ACC/Fluorocouncil), Steve Korzeniowski (Fluorocouncil), Marly Thomas (UML), Wendy Heiger-Bernays (BU)
Welcome and Introductions
Program Updates
- The RFP is out for grants for FY 2018.
- The spring CE Conference was held on 4/6/17.
- The Champions of TUR event at State House will be held June 20.
- Four Form R/S Workshops were held around the state in the month of May.
- SAB Members should submit their travel reimbursements for FY 2017.
Approve March Meeting Minutes
The March minutes were approved as written.
Vote: 6 in favor.
PFHxS/PFHxA Continued Discussion
At the January meeting, the Board voted to list PFOA/PFOS and their salts based on PBT endpoints. At the March meeting, we continued discussion of human health effects of PFOA/PFOS and introduced PFHxS and PFHxA.
PFHxS
The EHS summary for PFHxS has been updated to address comments from the last meeting. Focus areas were identified at the March meeting, studies were organized on the LibGuide by those endpoints and members were assigned to specific endpoints. Heather highlighted the areas that were updated and some key points.
PBT
For this endpoint the Board focused on persistence, bioaccumulation, and toxicokinetics.
With regard to persistence, the Board felt the evidence was solid and straightforward – PFHxS is very persistent (VP) and not expected to transform or degrade, and there is evidence that it binds to protein, similarly to PFOS. The evidence for bioaccumulation and biomagnification is not as strong as for PFOS. The bioaccumulation information from the SVHC document for PFHxS noted particular concern for mammals. A Board member noted that there were mixed results with regard to bioaccumulation. The question was raised as to whether the substance was bioaccumulating in the typical way, or rather building up over time due to the persistence and long half-life in the body. The Board noted a number of calculated BMFs > 1, indicating potential for biomagnification up the food chain. They also highlighted that there were clearly measured levels in serum and tissue, suggesting accumulation, although there was also a lot of uncertainty in the studies. There was more evidence for accumulation in biota for PFHxS (compared to PFHxA). In general, it was noted that there are differences in toxicokinetics depending on chain length, sulfonate vs. carboxylate, species, and gender. It was noted that there is evidence of a very long half-life of 8 years in humans (Olsen 2007). Other studies confirm this. The trend looks to have longer half-lives than PFOA across species.
Reproductive/Developmental effects
Primary articles reviewed included Butenhoff, Joensen, Kjeldsen, Maisonet and Zhao. The Maisonet cohort showed the upper quartile [blood serum] with lower birth weight and heavier at 20 months – which is also seen in the rat studies. Zhao notes a reduction in testosterone in humans, which is interesting given that some animal studies show an increase in androgen receptor agonists.
Opposite effects are found in different species. Rat and human data are showing completely different effects in terms of enzyme inhibition (PFOS). Vongpachan (2011) shows species difference in avian neuronal cells. The C6 chain was most potent with regard to mRNA expression. The C6 chain is affecting thyroid responsive genes, increasing expression of some of these genes (on and off through neuronal development). There was potential for disrupting thyroid hormone responsive gene expression in neuronal cells.
In Joensen (2009) fewer normal sperm cells were seen in younger men. In Butenhoff (2009) no reproductive or developmental effects were noted. However, reduced body weight at the highest dose, liver effects and total cholesterol effects were noted in parental males. Kjeldsen (2013) showed PFHxS along with PFOA and PFOS induced ER transactivity and antagonized AR activity. Response was non-monotonic, which is not atypical
The Board noted the confounding issue of metabolism of cholesterol – which will affect the availability of any kind of steroid, could affect the enzymes, and/or the receptor itself. At hormone levels gender differences are seen, but also interaction of endpoints.
Endocrine/Thyroid
Jain 2013 studied six thyroid parameters for six different PFCs; different effects were seen on different thyroid parameters. An increase in TT4 was observed with an increase in PHFxS. Hypothyroidism was noted for PFOA only, but the trend is there for others. A Board liaison had reservations about how concentrations were calculated (as different molecular weights were involved) and therefore the ranking of the PFCs (Gorrachateguie (2014)). An effect seen suggests an interference of PFCs with membrane lipids. Vongpachan (2011) showed altered expression of genes.
Neurotoxicity
Lee & Viberg (2013) and Lee (2014) were noted. Lee & Viberg (2013) looked at a single dose exposure during the brain growth spurt. A lot of activity occurred during the brain development. The study noted altered proteins, which lines up with the idea of PFASs general affinity for proteins rather than lipids. Proteins are enzymes critical to cell signaling pathways which orchestrate the complicated neurodevelopmental process. Articles were looking at the underlying mechanism of action. There is still much unknown about the neurotoxicity of PFAS, although it appears that it may be a common effect across the PFAS class. More studies are needed.
The developmental window study was noted as dramatic. This included exposure to many different PFCs which caused impaired response inhibition (Note: PFHxS was the second most abundant in the blood). The Board would like to know if these effects are seen similarly in PFOA and PFOS.
Hepatotoxicity
Activation of PPAR-alpha was seen, there was higher activation in mice than in humans. There was a biological response seen, with some similar chain length dose dependent response effects over various concentrations in cell culture studies. PFHxS is less potent than PHFxA and also less potent than the longer chain substances (Wolf et al. 2008; Bjork & Wallace 2009; Lau 2007). It was noted that PPAR-alpha activation may affect pup development and have broader implications on the liver. A board member noted some similar liver effects across the class.
The Board would like to see information on liver effects from PFOA and PFOS exposure. Some of this is found in the 2014 and 2016 EPA reports. These will be repeated on the Lib Guide for the next meeting.
Immunotoxicity
For this endpoint the Board focused on studies with regard to asthma, allergy and antibody production from vaccinations. They noted the following effects in studies that were reviewed: effect on suppression of immune response; humoral effects; level of antibody production from vaccination (prenatal or postnatal exposure); and asthma. The Board noted a striking consistency in conclusions by different authors. The mechanism remains to be seen how exposure to these chemicals are making children more prone to allergic responses.
The Board would like to know if there are any animal immunotoxicity studies for PFHxS.
PFHxA
The EHS summary has been updated based on comments from the March meeting. Focus areas were identified at the March meeting, studies were organized on the LibGuide by those endpoints and members were assigned to specific endpoints. Mary highlighted the areas that were updated and some key points. PFHxA is very persistent (VP) and not expected to transform or degrade.
A visitor noted that PFHxA is an impurity as part of the manufacturing process and does not have known uses, rather occurrences. A visitor noted that the C6 acid is not an endocrine disruptor. A Board member noted they would like to see the Bull et al (2014) for the next meeting. There was a comment about Gannon (2011), an ADME study, which showed elimination from organs in 24 hrs. There was a question about the aquatic toxicity box, specifically the statement “production volumes are increasing”. This was a conclusion from Barmentlo (2015), yet industry noted they are moving to non-fluorinated alternatives.
PFBS/PFBA Introduction
Draft EHS summaries for both PFBS and PFBA were distributed. These C4 substances will be discussed further at the next meeting.
Next Meeting
Wednesday, September 27, 2017, Location: TBA
Handouts
Updated Draft EHS Summary for PFHxS
Updated Draft EHS Summary for PFHxA
Draft EHS Summary for PFBS
Draft EHS Summary for PFBA
PFHxS – excerpts from Annex XV Identification of PFHxS as SVHC – March 2017