May 18, 2016
Toxics Use Reduction Institute Science Advisory Board Meeting Minutes
May 18, 2016
Tufts Sackler Library, Room 507, 145 Harrison Avenue, Boston
12:00 PM
Members present: David Williams (Chair), Larry Boise (Vice-Chair), Kenneth Weinberg, Christy Foran, Hilary Hackbart, Robin Dodson, Christine Rioux, Amy Cannon
Program staff present: Mike Ellenbecker (TURI), Heather Tenney (TURI), Mary Butow (TURI), John Raschko (OTA), Liz Harriman (TURI), Tsedash Zewdie (DEP)
Visitors: Denise Kmetzo, Katherine Robertson (MCTA), Richard Fitzpatrick (Kreussler), Sheilagh Fitzpatrick, Margo Simon Golden (MA Breast Cancer Coalition), Molly Jacobs (LCSP), Tricia McCarthy (Coyne PC for ACC), Margaret Gorman (ACC), Tracy Guerrero (SEHSC), Kathy Plotzke (SEHSC), Michelle Andriot (SEHSC), Wendy Koch (SEHSC)
Pre meeting presentation – Nanomaterials
Mike Ellenbecker and Molly Jacobs presented about current issues with nanomaterials. The focus was on current state of the science regarding toxicity of carbon nanotubes; known uses and policy issues were also covered. There is concern about the asbestos like effects of carbon nanotubes--- the fiber morphology may be important.
NIOSH is currently looking for markers of exposure – e.g. oxidative stress. There have been studies showing evidence of acute exposure inflammatory response and also mesothelioma.
Welcome & Introductions
Program Updates
- Form S Reporting Trainings: 2 have been completed, the 2 remaining on 5/26 Chicopee, 6/2 Newburyport
- Ethyl Acetate (EA) Policy Analysis was presented to the Advisory Committee (AC). The Board assisted TURI with the recommendation of EA as a Lower Hazard Substance (LHS) in December 2013. The Board noted concerns due to the flash point of EA. The Advisory Committee shares these concerns, particularly for facilities that may switch from a non-flammable substance to Ethyl acetate. The policy analysis is available on the library guide.
- June 8 – Honoring Champions of Toxics Use Reduction event at the State House.
Approve March Meeting Minutes
Note the positive animal study on page 3 under Carcinogenicity as ‘positive’ instead of “+”
Vote: 7 approve, 1 abstention
D4 Octamethylcyclotetrasiloxane – continuation of discussion
To date: The Board previously looked at D4 a few years ago. As the Board recently completed a review of D5, it made sense to consider D4 now as there is some overlapping information. The Board and Program staff members were split into 3 groups to cover the following topics: PBT, Metabolites, and Estrogen/Reproductive issues.
PBT.
- The Board noted that D4 meets the persistence criteria for air and sediment, but does not meet the half-life criteria for persistence in soil and water.
- D4 meets the toxicity criteria; it is classified as toxic to aquatic organisms at very low concentrations; Canada notes that it is very toxic to sensitive aquatic organisms.
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D4 does bioconcentrate, but in general, does not appear to biomagnify for most trophic systems.
Biomagnification field studies are difficult to interpret due to the many variables (season, temperature, species assumed to be part of the trophic system, etc…) and assumptions made in adjusting raw data for lipid normalization, etc. to calculate a TMF (trophic magnification factor). - D4 has also been found in wastewater effluents at similar concentrations, with the highest concentrations found at discharge points [Environment Canada 2008]. The substance was found in different locations in Ontario, US (Louisiana), at concentrations above the lowest-observed-effect-concentration (LOEC) of 0.0069 mg/L [Environment Canada 2008]. Note that these high concentrations are typically seen near wastewater discharges.
- The EU considers D4 to be a PBT and vPvB, and has recently approved a UK proposal to restrict its use (along with D5) in wash off personal care products.
In summary, the Board notes that D4 is very persistent in sediment and air, is bioaccumulative, but does not tend to biomagnify (pg. 21 UKHSE 2015). The Board noted that D4 is very toxic to sensitive aquatic organisms. The Board noted high variability in biomonitoring data, including temporal trends. SEHSC noted that they are in process of an Enforceable Consent Agreement with U.S. EPA. . There is monitoring data currently being collected at 14 sites.
Metabolites. There was not a lot of data or difference in the toxicity profiles. SEHSC noted that the ability to be metabolized may differ between D4 and D5. The toxicological profile accounts for the parent and the metabolite.
Endocrine and reproductive effects.
D4 is known to be a partial agonist to the estrogen receptor. In vivo effects are interesting, yet the results are varied. D4 interferes with timing of the luteinizing hormone (LH) surge, implantation ratios, and frequency of successful ovulation. Multigenerational study showed no effect in males.
The Lee study used a calcium binding approach. A change was not seen in uterine weight, which could be attributed to dosing the animals differently. There was a significant difference in body weight on the postnatal age, day 21. A statistically significant difference in body weight for Fischer 344 rats was seen on PND 23-24-25, not 22 or 26, so it occurred in the middle. A Board member noted that the dose response profile looks like that of BPA in terms of estrogenicity (Quinn 2007a). This was an in vitro/in vivo study, the units differed for BPA and D4, yet the profile looks similar. D4 starts lower and ends lower.
SEHSC noted that part of the challenge in assessing these effects is that they believe that they are non-specific membrane effects. These could be perturbing something that is having a downstream effect. They noted that even in males if there was a weak estrogenic effect, you would see something in the 2-generation studies, yet nothing is seen. Markers are not consistent for the very weak estrogen. The reproductive effect was clearly linked to the LH surge. There was decreased implantation and decreased number of pups. The LH surge is very different in animals and humans (e.g. can be linked to light and other things).
D4/D5 long term high level exposure interferes with pituitary signaling. The downstream effect is seen more with D4 than D5. Prolactin is affected.
Summary: Many reproductive effects seen – but were not consistent across all studies. Effects were not consistent between in vitro and in vivo. D4 has been associated with reproductive impairment (at certain exposure levels). There is no consistent marker for the mechanism for that impairment. Studies show that there is an estrogenic response at least in vitro. There have been non- specific changes in pituitary function. Hormones having varied changes that could be consistent with change in pituitary function. There is clear evidence of changes in timing and height of the LH surge. These are all rat models – applicability to human reproduction is not clear. Weak estrogenic effects are consistent, whereas anti-estrogenicity is less consistent.
Dibutoxymethane
This is the first meeting for the Board to begin discussing dibutoxymethane, the solvent in the commercial dry cleaning product Solvon K4 (SK4). Since this chemical is part of the Alternatives Assessment for dry cleaning, TURI brought information to the Board that is new since the assessment was completed. The Program is looking for any updates that should be made to the table in the alternatives assessment. The GreenscreenTM was reviewed and comments on the surrogates used were made.
Background information was provided on the use and disposal of dry cleaning solvents and TURI’s grants program for dedicated wet cleaning. A visitor representing the Solvon K4 vendor noted that SK4 is 99.85% pure dibutoxymethane (DBM). DBM is not a high production volume product. It is produced in Belgium and the United States, by two companies, both of which produce less than 1,000 tons per year. Most of the substance is used in the dry cleaning sector as SK4. The visitor noted that they produce a certificate of inspection on the batches that notes the byproduct of water and butanol as ingredients. They look for butanol and formaldehyde as impurities. There is a hydrolysis reaction of formaldehyde and butanol, where butanol is a residual co-reactant. A Board member asked how drycleaners dispose of the materials. The visitor noted that all are using modern drycleaning machines. These machines employ a closed loop dry to dry system where solvents are passed through textiles and a filtering mechanism. Contact water that comes out of the machine can go down the drain.
While the REACH registration dossier data noted the substance in non-flammable, additional information notes that has a flash point of 62°C. TURI will confirm this endpoint and then revise the alternatives assessment to reflect current data (sheet currently notes ‘combustible’).
The Board asked about the rationale for choosing the surrogates. It was noted that basic rationale is indicated in the relevant sections of the GreenscreenTM – EPA’s Analog Identification Methodology was used. TURI will create a table to compare the surrogates to DBM in terms of toxicity and will include additional information on EPA SAR rationale on the Lib Guide.
Kreussler would like to perform a mammalian mutagen study, and a reproductive study is forthcoming.
Board Members will follow up on the following endpoints:
- Analogs and mutagenicity – Chris & Larry
- PBT data – Ken, Dave & Amy
- CNS and Reproductive Effects - Hilary, Robin & Christy
The NIOSH study and mutagenicity studies will be added to the Lib Guide.
Upcoming SAB Items
The Program is interested in feedback from the Board with regard to using GreenScreenTM assessments as an initial overview for chemicals of interest moving forward. The Board discussed some of the issues, including surrogates.
Heather also asked if the Board would like to review and/or update the SAB Decision Making Principles from the Decision Making Document.
Next Meeting
June 27 – 12:30 pm – Location TBA
Handouts (limited copies available)
Nanomaterials presentation
PBT 1- page for D4/D5
Endocrine/Reproductive Effects for D4 1-page
SEHSC D4 Presentation
Solvon K4 EHS Summary
Solvon K4 GreenScreenTM