January 7, 2015
Toxics Use Reduction Institute Science Advisory Board Meeting Minutes
January 7, 2015
Massachusetts DEP, Conference Room A
12:30 PM
Members present: Dave Williams (Chair), Larry Boise (Vice-Chair), Christine Rioux, Robin Dodson, Kenneth Weinberg, Hilary Hackbart, Amy Cannon
Others present: Mary Butow (TURI), Liz Harriman (TURI), Mike Ellenbecker (TURI), Heather Tenney (TURI), John Raschko (OTA), Carol Rowan-West (DEP), Rick Reibstein (OTA), Tsedash Zewdie (DEP), Trisha McCarthy (ACC), Steve Rosario (ACC), Ralph Parod (BASF), Sean Moynihan (MCTA), Sahar Osman-Sypher (ACC), Tim Feeley (Bayer MaterialScience LLC), Elise Pechter, Richard Clapp, Bill Coyne (Coyne PC for ACC)
Members not present: Igor Linkov
Welcome and Introductions
Program Updates
• An updated Methylene Chloride fact sheet was distributed to the Board.
• New members of the Advisory Committee were announced.
• New members of the Administrative Council are still pending.
• OTA noted that the fees regulations are still at the Governor’s office.
Approve September Meeting Minutes
Two typos were noted; one in the Program Updates section, the other in the first paragraph of the Diisocyanates Category section.
Vote: Approved (as amended): 6 in favor, 1 abstention.
Toluene Diisocyanate Comments
Program staff reviewed the HHS process for the 5 substances recommended for designation as HHS in the Fall of 2014. There were many comments on TDI and very few comments on the other four. Regulations are in process for the other 4 substances. There is currently an additional 60 day public comment period for TDI. As part of this additional public comment period, we are asking the SAB to review studies and information cited in comments received to date. A LibGuide was prepared for the SAB’s use with applicable excerpts of comments received during the public comment period, all referenced studies, and many additional supporting studies. The current question for the Board is “Do you see evidence that would lead you to change TDI’s categorization as a More Hazardous Chemical?”
The Board chair invited guests attending the meeting to make brief comments regarding this question if they wished, prior to the Board’s discussion.
- Ralph Parod (toxicologist with BASF) said that he did not believe that a recent objective review of data had occurred, and reiterated his written comments that had been submitted during the original public comment period, critical of the process and TURI documents. He also reiterated his comment that the NTP carcinogenicity study of TDI, on which IARC and NTP based their designations, was flawed. He offered that key hazards of TDI were irritation of the skin, eyes, and respiratory system, and contact dermatitis and asthma in some individuals.
- Tim Feeley (industrial hygienist with Bayer MaterialScience) provided comments from ACC’s Diisocyanates Panel. He said that while they recognize the SAB is focused on inherent hazard, they feel that other use, exposure and risk issues were not sufficiently considered in TURI’s policy analysis. He reiterated comments made during the original public comment period regarding end uses, lack of technically feasible substitutes, number of facilities impacted, and industry product stewardship initiatives. He noted that while the use of TDI has increased, occupational asthma from TDI has decreased. Regarding the ACGIH TLV exposure limit Notice of Intended Change referenced in TURI’s policy analysis, he clarified that the notice lowering the TLV was issued 8 years ago, and he believed that it had not yet been changed because of the comments provided by the Diisocyanates Panel to ACGIH.
A Board member asked if Mr. Parod considered TDI to be a sensitizer, and he answered yes.
- A visitor noted that TDI is a sensitizer and recent information on the mechanism of action is referenced in Anderson, et al. 2014. Regarding carcinogenicity, he/she offered that TDI is still recognized as an animal carcinogen, and is transformed to TDA in the gut. IARC human epidemiological studies indicate some excess lung and pancreatic cancer, yet overall the results are equivocal. In their estimation IARC’s 2B is the correct designation with regard to carcinogenicity. He/she also suggested that the recent CA OEHHA review on the toxicity of TDI was a good resource.
- Regarding carcinogenicity of TDI, another visitor disagreed and said that TDI is metabolized to genotoxic TDA in the gut, but only if it gets there. When TDI interacts with biological fluid, it instantaneously interacts with proteins. It was stated that one only finds TDA when directly injected into low pH environment of the stomach and this doesn’t occur by normal biological/physiological mechanism. Prueitt 2013 discusses epidemiological studies in detail. The visitor noted that the only positive result for cancer is the NTP study and questioned why other diisocyanates aren’t classified by IARC if the isocyanate moiety is what is responsible for TDI’s carcinogenicity.
- Program staff noted that sensitization was the critical endpoint, and reviewed the SAB’s original decision to categorize TDI as a More Hazardous Chemical. The categorization listed irritation of the eyes/nose/skin, the TLV of 5 ppb, and the IARC 2B status. The reason for ACGIH’s very low threshold limit value (TLV) is concern for allergic sensitization of the respiratory tract and asthma. Another study was referenced citing the early Massachusetts experience with TDI and sensitization in MA workers (Elkins 1962).
- It was also noted that health effects are difficult to study when workers are leaving due to sensitization. A visitor noted that sensitization at 5 ppb is to protect all workers as not everyone becomes sensitized, only some individuals with a genetic link. He/she stated that only 2 individuals in the state of MA from 2009-10 developed occupational asthma (NIOSH 2014) due to TDI exposure.
- Visitors had comments about the process by which the recommendations of the SAB are made and about the process and potential regulatory actions with regard to the More Hazardous Chemical list moving forward. Program staff reviewed the process by which the More Hazardous Chemical list was created and how that list relates to potential Higher Hazard Substances.
Board Discussion of TDI Literature Review
Sensitization:
Several Board members noted that there was nothing new suggesting the inherent hazard of TDI as a sensitizer has changed since TDI was categorized as a More Hazardous Chemical by the SAB. One member noted that there was a change in focus of studies over time. After 2000 there are many epidemiological studies and asthma studies. It was noted that sensitization is still being seen in workers where modern engineering controls are used (Gui 2014). The Board member noted that there has been no change in the inherent hazard, but the industrial hygiene has improved. The mechanistic information regarding miRNA unfortunately does not tell about sensitization in humans (Anderson 2014).
Another Board member noted there was no change showing a reduction in inherent hazard, but there have been reduced rates of sensitization from better exposure controls. They also noted that OSHA recently implemented the Isocyanate Exposure National Emphasis Program (NEP) in 2013, and also mentioned concern over accidents, and a SENSOR fatality in Michigan. A Board member also noted that the exposure levels being very low speaks to the issue of OSHA’s emphasis on TDI and their current RFI for revision of levels.
- A visitor noted that a contact of theirs from the OSHA NEP program indicated very few citations regarding over-exposure to isocyanates. Another visitor noted that there have been some OSHA citations in Massachusetts regarding detectable levels of TDI back to 1990 (9 companies). It was noted that a MA company was cited in a 2011 OSHA inspection for respiratory protection standard violation.
A Board member noted that some epigenetic articles had been identified. They also shared other concerns including the fact that skin exposures can result in respiratory reactions and that effects from exposures may appear later (latent effects). The Board member did not find any evidence that would cause them to reconsider the MHC categorization.
Carcinogenicity:
A Board member noted that the Prueitt article highlighted the question about route of inhalation, and noted epidemiological evidence with both positive and negative effects, and hence determined the data to be equivocal. Another Board member noted that it is still listed as an IARC 2B (possibly carcinogenic).
- A visitor noted that although the substance is currently listed that way, recent papers are in disagreement and this needs to be followed up on. The current NTP designation of “reasonably anticipated to be a human carcinogen” was due to dosing directly to the rat stomach (by oral gavage). A comment was made that when TDI is inhaled (a typical route of exposure), almost all of it goes through the gastrointestinal tract. As additional evidence of TDI’s inability to reach the stomach through ingestion, a visitor noted an instance where intentional ingestion of a large quantity of TDI had produced an immediate reaction into polymeric material throughout the esophagus.
A Board member noted that there was some slight evidence of increased lung cancer in women (Prueitt 2013).
Other effects:
A Board member noted that there was not strong evidence for neurotoxic effects (Hughes 2014). There was also not much evidence for TDI’s genotoxicity and it appeared to have the same issues as carcinogenicity. Program staff noted that there was not a lot of information on reproductive and developmental toxicity.
Summary
SAB members were asked if they thought TDI should not be categorized as a More Hazardous Chemical (i.e., should its categorization be changed), and none present did.
Program staff will update the Administrative Council regarding this discussion and will update the wording in the Policy Analysis.
CERCLA Categories: Phthalate esters
The Board unanimously voted to table discussion of the Phthalate esters until the next meeting.
Diisocyanates Category: Review of Component Substance Data
Review of this category will resume following the completion of work on the Phthalate esters.
Next Meeting
Wednesday, March 11th, 12:30PM
Handouts:
• TURI – Methylene Chloride Fact Sheet