December 6, 2017
Toxics Use Reduction Institute Science Advisory Board Meeting Minutes
December 6, 2017
Massachusetts Department of Environmental Protection – 2nd Floor, 1 Winter Street, Boston
12:00 PM
Members present: David Williams (Chair), Larry Boise (Vice-Chair), Denise Kmetzo, Christy Foran, Ken Weinberg, Robin Dodson, Chris Rioux, Hilary Hackbart
Members not present: Amy Cannon, Wendy Heiger-Bernays
Program staff present: Liz Harriman (TURI), Heather Tenney (TURI), John Raschko (OTA), Mary Butow (TURI), Tsedash Zewdie(DEP)
Others present: Patricia McCarthy (Coyne Legislative Services for ACC), Margaret Gorman (ACC), Jessica Bowman (ACC/Fluorocouncil), Steve Korzeniowski (Fluorocouncil), Devin Savaskan (O’Neill and Associates - MCTA)
Welcome and Introductions
Program Updates
- TURI will be moving to Boott Mills in Lowell, estimated move date is mid-January 2018.
- TUR Planner Continuing Education Conference was held in Taunton, Thursday, November 16, 2017.
- RC planning will be offered this February in Lowell
- OTA Resiliency Trainings are ongoing.
- There will be a webinar on nanomaterials featuring Molly Jacobs and Dr. Michael Ellenbecker at noon on December 7, 2017. TURI has also released a nanomaterials fact sheet and OTA is currently administering a nanomaterials survey.
- DEP has sent a letter to filers notifying them that 2018 is a planning year
- P2OASys has been released in a beta version.
Approve September Meeting Minutes
The September minutes were approved as written.
Vote: 8 in favor
PFAS Continued Discussion
Studies from the table distributed at the last meeting were integrated into the substance specific EHS Summaries along with information submitted from ACC in the ENVIRON report. Input is welcome regarding information missing or that can be deleted. From this point forward we will use the EHS summaries in considering the specific PFASs.
PFHxS:
The board discussed the EHS summary and key points for PFHxS.
Regarding neurotoxicity there is evidence for ADHD association. A member noted items from their previous notes (on the LibGuide) that should be added – e.g. some negative studies such as Wang 2015 which showed no evidence of lower IQ. There may be more information from Zhang 2011 as it was a basis for TX water values. There is clear evidence for pathways for neurotoxicity and apoptosis of neuronal cells as seen in neurodegenerative diseases. PFHxS shows developmental neurotoxicity.
For developmental and reproductive toxicity there are a couple of studies showing changes in lipid metabolism related to steroid production. It was noted that epidemiologic studies pertain to PFAS mixtures, as people are exposed to many fluorinated compounds. However, when researchers have separated out PFHxS it shows effects. Maisonet 2012 showed reduced birth weight and Joensen 2009 showed reduced sperm count. Watkins 2015, a positive gene expression study, showed changes in enzymes in steroid production. Board members questioned the results shown in Wang 2017 - they should be reviewed more closely.
For endocrine and reproductive effects there is some evidence across studies that PFHxS is as potent as PFOS and PFOA. These are very important endpoints in terms of biological activity and are as concerning as PFOS/PFOA with longer half-lives. The thyroid piece is interesting in terms of toxicity and should be looked at in a broader toxicological context.
Regarding immunotoxicity, the Grandjean study showing reduced antibody response is interesting, but it is hard to link to a particular compound.
For liver toxicity, information from Wolf and Butenhoff is relevant. There was a mix of conclusions about what effect it has on cholesterol levels, but effects were seen across studies. The significance to other systems was questioned – this is a complex pathway. For PFOS and PFOA, EPA studied PPARa null mice (Das, et al 2017). PPARa is expressed in every tissue, not just in the liver, and it is relevant to humans. The sulfonates may not be as important for PPARa as carboxylic acids.
Dong 2013 showed an association between PFHxS and asthma.
Regarding toxicokinetics, PFHxS has a very long serum half-life in humans (7.3-8.5 yrs) – twice as long as PFOS/PFOA. The half-life is shorter in rodents than humans (thus rodent studies may not capture effects). PFHxS is persistent. There is evidence for bioaccumulation in many species and biomagnification in many predator-prey pairs. Most results are >1 (indicating potential for bioaccumulation), with some fish study results <1 (indicating low potential for bioaccumulation).
For human health and risk values there are additional standards not shown on the EHS summary which are relatively low for PFHxS, some are lower than for PFOA and PFOS.
It was suggested that the ITRC (Interstate Technology Regulatory Council) newly published PFAS fact sheets might be helpful.
PFHxA:
There may potentially be a use of PFHxA, ACC will send us that information.
Regarding neurotoxicity there were no significant findings. One low dose study showed an effect with no dose response. For reproductive and developmental toxicity there were high dose effects on pups – less so for PFHxA than for PFHxS. There was some evidence, but it was not as strong. There appears to be a discrepancy in the NICNAS reports with one showing a proposed classification as a developmental toxin yet the PBT report showing it as not “T”. TURI will look into why those documents differ.
Regarding endocrine/thyroid effects, potential activity was noted but it was much less potent and potentially goes in both directions. The SETAC poster from ACC was distributed. ACC will look into getting us the unpublished studies referenced on it. They are working on a paper for a journal now. The Program will add Ren 2015 and 2016 papers to the LibGuide. Kim 2015 was noted and it was noted that non-monotonic dose responses may be expected for endocrine effects.
It was questioned why there are so many more studies on PFHxA. ACC noted that a lot of studies were mandated under their consent order with EPA, for example their 2-year cancer study (Klaunig). These studies are often protected/CBI. Several companies have decided that all their data will go to peer reviewed journals, but companies can choose to keep their data secret. It was noted that there is probably a lot more information out there that we cannot access.
In looking across substances, a board member noted that PPARa activity was indicated as a general effect (Wolf 2008, and Danish EPA p. 28-29). In the LOAEL box on the EHS summary, check the original reference from Danish EPA regarding relative PPARα potency of carboxylates and sulfonates and correct if necessary.
The Dong study which studied associations for several PFAS showed no association with asthma for PFHxA. It was noted that it is the only one that showed no association and it had an odd P value.
NOAELs from ENVIRON referenced the kidney. We had identified kidney effects as of potential concern prior to the literature review but had not found many studies.
Toxicokinetics – Russell 2013 indicates an apparent elimination half-life of 14-49 days. ACC notes that the half-life in Russell is derived and it is too short to measure in humans. Gannon 2011 (rodent study) shows 100% clearance in 24 hours.
It was noted, generally for all PFAS, that all epidemiologic studies are mixtures and there are likely synergistic or additive effects. A visitor also noted that PFHxA is an impurity in the PFHxS manufacturing process.
PFHxA is persistent. Studies show low potential for bioaccumulation of PFHxA in most biota, although there are concerns about accumulation of precursors that then transform into the acids. Concerns were noted for bioaccumulation in invertebrates/earthworms. Is there further information available? In the cyanobacteria study 10 micrograms/l for bluegreen algae seems low and concerning. There was also a frog embryo assay that suggested PFHxA could be a developmental toxin/teratogen. A member asked the DEP representative if they had developed a standard for PFOS and the additional compounds.
ACC noted that a GreenScreen assessment has been done for PFHxA. They will send it along and ACC will also send the French reference dose.
PFBS:
The 1982 Bayer study shows a low LD50 - this number was questioned. It is out of range with other LD50s for this substance and other PFAS. The year will be added to the EHS summary.
The implications of impaired function of neurotransmitters seen in Slotkin 2008 were questioned. Slotkin 2008 will be added to PFAS Literature Guide, “CNS/Neurotoxicity” tab.
For developmental and reproductive toxicity, the 2017 Wang study was questioned again. The concentrations overlap, there was a low sample size, and it was nearly as likely to be a control as a case. It was noted that there is not a lot of concerning evidence for reproductive and developmental toxicity.
Regarding endocrine and thyroid effects, PFBS disrupts the equilibrium between androgens and estrogens. It interferes with all the balances between steroids and lipid metabolism. There is potential endocrine disruption.
Regarding immunotoxicity, some interaction was noted in the Corsini study. Dong showed an association with PFBS and asthma, however previous concerns with this study were again noted.
Regarding toxicokinetics, half-life in humans is 25 days. Half-life in animals is less than humans, but the lifetime of animals is less too. The DEP representative cited a 2017 Japanese study for half-life. They will get it for us.
For PBT –Bioaccumulation TURI will research sources for material in the first paragraph of the bioaccumulation box on p. 10 regarding fluorotelomer accumulation (Danish EPA) and "not bioaccumulative or toxic to aquatic organisms" (Dewitt).
PFBA:
PFBA will be deferred to next time due to time constraints.
PFAS: Precursors and range of substances:
Liz distributed the category document outlining known precursors and how other governments are handling them. The substances we are looking at now are the ultimate breakdown products and not necessarily what is in commerce. There are direct precursors which are generally the anhydrides, salts and basic halides and then there are more indirect precursors such as polymers. There are several references regarding this on the LibGuide: UNEP Global Synthesis paper, NICNAS description, and Norwegian Environmental Agency background. If we recommend listing these specific PFAS, we may want to consider listing their precursors. For PFOA and PFOS we have already recommended listing their salts along with them. It was noted that it is important to consider the policy implications regarding reporting of substances as a category. Toxicity studies of the precursors were requested.
Next Meeting
Wednesday, January 10, 2018
Handouts
- Updated Draft EHS Summary for PFHxS
- Updated Draft EHS Summary for PFHxA
- Updated Draft EHS Summary for PFBS
- Draft – PFAS Substances Including Direct and Indirect Precursors Background Information
- SETAC Poster – ToxStrategies, Borghoff SJ, et al. “The potential for PFHxA to modulate the endocrine system in wildlife: A hypothesis-driven weight-of-evidence analysis across endocrine pathways”. Limited copies.
This information was posted to the website on Wednesday, March 28, 2018.