March 29, 2017

Toxics Use Reduction Institute Science Advisory Board Meeting Minutes

March 29, 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, Chris Rioux, Christy Foran, Ken Weinberg, Hilary Hackbart, Robin Dodson

Members not present: Amy Cannon

Program staff present: Liz Harriman (TURI), Heather Tenney (TURI), John Raschko (OTA), Tsedash Zewdie (DEP), Mary Butow (TURI)

Others present: Tricia McCarthy (Coyne Legislative Services for ACC), Katherine Robertson (MCTA), Margaret Gorman (ACC), Jessica Bowman (ACC), Konrad Kulacki (Exponent)

Welcome and Introductions

Program Updates

A document with several updates from the Program was distributed. Information included:

  • TDI is a HHS as of Reporting Year 2017; in July 2018 companies will have to report TDI for 2017 if their use exceeds the 1,000 lb threshold.
  • Spring CE Conference 4/6/17
  • May 10 – Greener Materials Research Symposium
  • June 20 – Champions of TUR event at State House

Approve January Meeting Minutes

Minutes approved as written.

Vote: 5 in favor, 3 abstentions.

PFOA/PFOS Human Health Effects

At the last meeting, the Board recommended to list PFOA/PFOS and their salts based on PBT effects. The Board had prepared to discuss human health endpoints, but ran out of time for that discussion, so those topics were moved to the agenda for this meeting. Human health effects were broken into groups for cancer, thyroid/endocrine, and “other”. Those effects were discussed with an eye toward what may be seen in the other PFAS. Information submitted in response to the call for information was highlighted in green text on the Lib Guide.

Cancer – The cancer effects had been discussed briefly two meetings ago. The C8 study was reviewed at that point and a table with effects seen was distributed. Since that time the IARC (2B) monograph was added to the Lib Guide as well as the Chang review article that Ken identified. Members noted definite links and associations with certain types of cancers for PFOA, whereas information is lacking for PFOS. The difference between effects for sulfonates and carboxylates may be a difference in mechanism of action of the chemicals. The mechanism is an outstanding question.

A member commented that they found the information fairly compelling. While breast cancer information is not included here, there is influence on mammary gland development that is well documented in the New Jersey report. It was noted that there is not a regulatory framework for breast cancer caused by in utero exposure. Some observed abnormalities are associated with increased breast cancer risk.

There was a discussion regarding altering mammary gland development in utero and potential breast cancer development.  TURI will check for additional studies on this specific endpoint. It was questioned whether the effect on mammary gland development is also seen in testicular development?

A member commented that the 2B IARC classification seems to be appropriate. The U. S. EPA Science Advisory Board classifies it as likely to be carcinogenic, (Board member noted this from the NJ Drinking Water Quality Institute’s Health-Based Maximum Contaminant Level Support Document for Perfluorooctanoic Acid (PFOA)). Suggestive evidence of carcinogenic potential by EPA’s Office of Water.

Thyroid/Endocrine Effects - Although various thyroid effects are seen in most studies reviewed by various groups, thyroid hormone levels, when measured, are not found to be altered consistently in one direction (some show decrease in T4 and increase in TSH (signs of hypothyroxinemia or hypothyroidism), while others show the opposite effect (increase in T4 and decrease in TSH (signs of hyperthyroidism)). However, the available animal studies consistently show decreases in T4 and increases in TSH, suggesting that the effect of PFOS/PFOA on the thyroid may probably lead to hypothyroxinemia or hypothyroidism.

Males and females may respond differently to the effects of PFOS and PFOA on the thyroid. In one study the data showed that males with higher PFOS levels were more likely to report currently treated thyroid disease than males with lower PFOS levels. Females had lower levels of PFOS than males and higher prevalence of thyroid disease (from Table 3-6, see handouts section). With PFOA, the opposite was found, with females with high levels, but not males, more likely to report thyroid disease.

It appears that shorter chain substances are potentially more potent on the mRNA expression. Vongpachan 2011 notes short chain PFCs less than eight carbons altered the expression of TH-responsive genes. It was noted that the binding potency of even carbon chain substances was more potent than the odd, and smaller carbon chain lengths were more potent than the longer (Weiss 2009). This could be due to steric issues. Given this, it will make sense to touch back on thyroid effects during the discussion of short chain PFAS.

Other Effects

Immunotoxicity – Heather highlighted the NTP monograph regarding immunotoxicity for PFOA and PFOS, the Grandjean 2016 study and Dr. Chang’s review of immunotoxicity studies for PFOA and PFOS.  Discussion noted that there is evidence of immunotoxicity for both animal models and different human populations from different areas, for both PFOA and PFOS and perhaps other PFAS. The mechanism -- suppression of an antibody response -- has been identified. In animal models lower natural killer cell activity is observed. Grandjean work is very interesting as well. Will leave the Chang article up on the Lib Guide for the next meeting. NTP monograph also interesting.

PIH- A member commented that Pregnancy Induced Hypertension had insufficient data based on their review.

High cholesterol - Is it considered a toxic response? The C8 panel showed elevated cholesterol in humans while animal studies showed a decrease.

Autoimmune (Ulcerative Colitis) - For the probable link setting for C8 work, they just indicate a connection, not necessarily causal. The mechanism has not been identified.

PFHxS and PFHxA Introduction

EHS summaries for PFHxA and PFHxS were prepared for this meeting.

PFHxA - Mary reviewed the PFHxA draft EHS summary. Ms. Bowman noted that PFHxA is not intentionally manufactured. 

Perez 2013, which analyzed presence of 21 different PFAS in cadaver tissues, was noted.   Of particular concern for PFHxA were the results in brain tissue.  Ms. Bowman offered to send comments on the analytical methods used in the Perez study.

Ms. Bowman also offered to provide additional studies on other endpoints, mostly for PBT. PFHxA is extremely persistent similar to PFOA.

Moving forward the Board would like to look more closely at PBT endpoints (including bioaccumulation in terrestrial plants), thyroid effects, immunotoxicity, hepatotoxicity and developmental toxicity.

PFHxS – Ms. Bowman noted that the ACC FluoroCouncil considers PFHxS a long-chain and offered to submit follow-up information on the classifications of C6.

Dr. Clapp highlighted this substance last time. It has been detected in drinking water at Pease Air Force Baseand in blood samples of children and adults there.

There were no LD50s identified. A TDLo -- lowest minimal dose -- was identified. Dr. Clapp had highlighted neurotoxicity effects as an endpoint to look at for this substance.  Developmental neurotoxicant effects are similar to that of PFOA and PFOS. It was noted that the C8 panel did not find a probable link for PFOA to ADHD. For developmental and reproductive toxicity there were some effects on birthweights and both male and female impacts. Pups were underweight at birth then weighed more afterward.  It was mentioned to look at fecundity as well.

The Kjeldsen 2013 study on mechanism of interference with steroid hormone receptor functions was noted.  It was also noted to change “metabolites” section title to “toxicokinetics,” as better descriptor of information, and as PFHxS does not metabolize.

PBT information. PFHxS is extremely persistent.  It has been detected frequently in biota and plants, but bioaccumulation patterns are not clear. Liz reviewed notes from the recent EU SVHC PBT document (see Handouts section below for title).  Numerous BMF >1 were calculated from several different predator-prey relationships, indicating biomagnification potential – there are significant uncertainties and assumptions, but as a whole they indicate a potential for biomagnification.  It was noted that these studies and results have a fair bit of uncertainty, as is typical for bioaccumulation and trophic magnification studies.  Complicating factors include: which tissues are sampled, organ vs. whole body concentrations, feces collected, diurnal and seasonal cycles, location and migration, etc. Note: Some results are reported as logs and some not, e.g., BAFsare reported as log BAF, not an actual ratio. BMFs reported in study are actual ratios.

Moving forward the Board would like to look more closely at PBT endpoints, neurotoxicity, thyroid effects, immunotoxicity (specifically asthma), hepatotoxicity and developmental/reproductive toxicity.

Heather will set up review teams for the next meeting.

Next Meeting

May 31, 2017

Handouts

  • TURA Program Update March 2017
  • Draft EHS Summary for PFHxS
  • Draft EHS Summary for PFHxA
  • PFHxS – excerpts from Annex XV Identification of PFHxS as SVHC – Mar 2017
  • Table 4-4. Association of serum PFOA with the prevalence of thyroid disease and thyroid hormone levels in studies of general and worker populations, from U.S. EPA 2014: Health Effects Document for PFOA.
  • Matrix of information from studies on Lib Guide re: thyroid effects
  • Table 3-6. Summary of Epidemiology Studies of PFOS and Thyroid Effects, from U.S. EPA 2016a: Health Effects Support Document for Perfluorooctane Sulfonate (PFOS).
  • Table 1. Summary of results from recent epidemiology studies focusing on PFOA and PFCs, from DEP 2016.
  • Probable Link Evaluation of Cancer, C2 2012a.
  • Probable Link Evaluation of Thyroid Disease, C82012b.
  • Other Effects Notes for PFOA and PFOA, TURI 2017.
  • Perez, et al 2013, Figure 1. Concentrations of various PFASs (in ng/g) in 5 human tissues from 20 residents of Tarragona (Catalonia, Spain).