June 9, 2009

Toxics Use Reduction Institute Science Advisory Board Meeting Minutes
June 9, 2009

Members Present: Larry Boise, Chris Swartz, Lorraine Braunsdorf, Hilary Eustace, Veronica Vieira, Dave Williams, Anne Marie Desmarais

Others Present: Heather Tenney (TURI), Mike Ellenbecker (TURI), John Raschko (OTA), Mary Butow (TURI), Glenn Keith (DEP), Mark Smith (DEP), Sanford Ostroy (Professor Emeritus of Biological Sciences from Purdue University), Dave Wawer (MA Chemistry Council)

Welcome and Introductions

Program Updates
· The Program is still awaiting the budget for next year.
· The next SAB meeting is planned for July 22nd; the Advisory Committee is meeting next door today. The Administrative Council will meet on July 29th. Decisions affecting regulations for this calendar year must be made by the end of July. Chemicals with revised recommendations, CERCLA categories, and nPB will be decided on July 29th. The groups will have August off.
· The nPB discussions, as well as the SAB guidelines, are the priorities for the next meeting. If time permits there will be a discussion on the splitting of the chromium compounds category.
· The TURI Statehouse event is tomorrow in the Great Hall.
· Next month is the 20th anniversary of signing of the TUR Act – the Program will be honoring that anniversary by having a symposium in the fall to celebrate the anniversary – 11/4 & 11/5 at a hotel in Burlington. The first day will be a Scientific Symposium, the second day will be more of a MA program focus.

Approve May Minutes
6 in favor and one abstention from member who was not at the May meeting.

n-Propyl Bromide
The n Propyl Bromide discussion was started. Decisions are planned to take place at the July meeting in order to give industry representatives time to provide data and/or make plans to attend. MCTA has been notified of the potential listing. It was noted that the Halogenated Solvents Industry Association should be notified as well.

One member raised concerns that reviewing only n Propyl Bromide was short sighted – it would be easy for manufacturers to switch to dibromopropane or another similarly halogenated compound, which may be equally hazardous. There was a proposal that instead of listing nPB – we list something called ‘certain halogenated compounds’ as a category. There was general consensus that this was an excellent idea and would save both industry and Board time in the future. The only concern raised was that defining the category and reviewing chemicals for it could be very time consuming and a decision on nPB was expected in July. It was proposed that a two phase approach be used: first, decide on nPB. Then define a category and make a decision on that. That way an nPB decision can be made in July and the group can still be proactive regarding the rest of the potential category.

Then, nPB as a singular chemical was discussed. The DEP information that Carol sent out was reviewed. Heather noted that nPB is not an IARC, although there are CNS issues, as well as developmental and reproductive concerns (as evidenced by its presence on the CA Prop 65 List and the EU CMR list). Mark noted that the information on nPB by DEP is currently only for internal distribution. Results from MTP carcinogenicity study are incomplete as they had not looked at the original results when first assembling the information. He noted that nPB and all possible related compounds are classic nucleophilic alklating agents. In his experience studying damage to DNA, he noted that the structure is of concern. The comparative toxicity data is weaker than PCE from the standpoint of human health effects, but from a listing perspective, that is not a concern and the data supports listing. This is still the case despite there being gaps in the carcinogenicity data base – he stated that there should be more information in the next few weeks. The reproductive effects are significant. A member questioned DEP in terms of their report in that it included review of other reviews of papers. Mark noted that they would not be able to dig into the primary literature by the next meeting. They do feel that the secondary sources cited are reliable and have a high degree of confidence in their accuracy.

The reproductive effects paper (IBSA) that was distributed was then discussed. OTA noted that it is an older paper and there is no date on the references- the most recent date indicated was 2003. There was a question as to whether the review suggested in the paper was ever completed. TURI will check on the status of the review prior to the next meeting. One member noted that if the review had found something significant, it would likely have been found in DEP’s review.

The Program will also look into why it has been listed on the CA Prop 65 list and the EU CMR list.
Several members expressed that they thought it belonged on the TURA list, even with the data gaps, and added that more literature is always welcome. Heather noted that anyone who thinks it should qualify as a HHS should consider that during the review of the remaining information.
Next, the concept of a halogenated compounds category was discussed. A definition might look something like this “ a compound containing 4 or less carbons and one or more of the elements fluorine, chlorine, bromine, or iodine”
Four representative chemicals were suggested for the category:

· Methylene Chloride
· Perchloroethlyene (Perc)
· n-bromopropane (nPB)
· Isofluorobutane

Three of the four suggested representative chemicals already have a lot of information available. Some of these are already on the list, but the brominated analogs are not on the list, as well as the fluorinated analogs. Heather noted that there may be some overlap with the other CERCLA categories. TURI will review possible overlapping. Members estimated there would probably be over 100 chemicals in the group. OTA inquired about a surrogate with iodine, perhaps iodoform. The reason indicated for not selecting that is iodine would be less reactive compared to chlorine/bromine.

There was a question as to a clarification of the function of representative chemicals. Essentially, representative compounds are selected for a category and conclusions are drawn about the properties of other similar compounds – ie glycol ethers. A member noted that similar structures most of time exhibit similar properties – molecular weight affects volatility – behavioral toxic properties tend to be similar. It was noted that in general halogenated compounds that are lighter are more reactive – longer carbon chains mitigate some of that. Some may be solids and not even a solvent.

Discussion of SAB Guidelines document
The SAB made guidelines in 1995 for companies requesting the listing/de-listing of chemicals. These guidelines were for decision making in regard to the petitions. It has been a long time since this document has been reviewed. Some of the information we evaluate is the same, while some has evolved from what is indicated.

Criteria we look at now:
· IARC
· PBT profiler (persistence, BCF, aquatic toxicity)
· Neurotoxicity
· Developmental/Reproductive toxicity
· LD50/LC50
· Reference dose
· MRLs
· NIOSH REL, TLV
· Flashpoint

The question was posed if there were any endpoints missing or unnecessary and also whether any endpoints could be added. Some labor representatives from the Advisory Committee have expressed a serious interest in having the following endpoints considered as a part of any chemical discussion: Asthmagens, Immunotoxins, and Sensitizers.

Someone noted that flashpoint and flammability were used least. A member noted more information could be added including molecular weight, water solubility, and structure. SAR studies on surrogates with same general molecular configuration are useful. Another member noted metabolite and degradation product information would be useful, as well as a summary of production and industrial uses in a table.

There was some discussion around indicating if substances are Asthmagens and/or sensitizers and how these would be characterized. Heather noted that TURI gave a grant to a UML group to research Asthmagens, specifically reviewing the mainstream lists and comparing them to the TURA list. There was discussion about defining sensitizers. A member noted that the response is substance specific, i.e. poison ivy or respiratory shutdown. Substances where there is huge individual variability are harder for extensive metrics. It is very difficult to establish a causal link, mainly because such a small segment of the population may be affected severely, vs. the rest with a ‘typical’ response.

QSTAR for carcinogenicity was previously considered and now we look at IARC for carcinogenicity. One member noted that we normally use the EPA guidance, IRIS, which the slope factors are a derivation from the QSTAR with risk expressed as an exponent. Dose response curves are available in IRIS, also from the Oakridge National Laboratories (ORNL.gov). The limitation with this laboratory is that it is not as peer reviewed as IRIS- it pulls in CA data and other information EPA hasn’t fully peer reviewed- but can be used in a database with notation.

If mammalian LD50 is available, it makes sense to have the LD50 on the list but there has to be some way of expressing the shape of the dose response curve. LD10 and LD90 are helpful in doing this if info is available in RTECS or CCRIS. For two chemicals with the same LD50 - one could be a sure killer with no margin of safety vs. others with a significant margin of safety. Acute effects – reference dose and rfc on subchronic level are as important as LD50.

Persistence data and BCF data are critical – when you deal with a substance that is going to hydrolyze or undergo photolysis, even if of equal toxicity. There was a question as to whether the PBT profiler information is helpful. Limitation with that data is that it is profiled. ORNL gives a subscript that it is not peer reviewed. PBT profiler does not do that, rather it uses surrogates. The structure activity relationship data is important information, which is part of why it has been considered in the recent past.

There was some discussion with regard to the difficulty (from a scientific perspective) of divorcing straight toxicity and use. There are clearly different possible applications, some more chemically stable than others (i.e. substances in concrete), and as such lifecycle analysis may be relevant. Not considering uses could lead to over-regulating something presenting minimal hazard, or under-regulating something that could result in considerable hazard.

Glenn noted that the Advisory Committee and the Administrative Council were not opposed to the SAB considering those issues. If the current draft of the document says they only consider hazard, then it is inconsistent (i.e. copper in a penny.) So, it is appropriate to consider the use of a material. He stressed that it is only important that the document reflects what they actually do. Currently it says the SAB only considers hazard. Glenn also noted that the primary focus is on inherent hazard, and it is human curiosity to discuss usage. Most comment about use at some point or another (where it is known). Mainly they can’t stay focused on using chemicals in isolated applications. John noted that in the historical discussions looking at use meant not so much what industries were using chemicals in manufacturing certain products, but how it was being used in a particular workplace. The potential for worker exposure was a big concern. A member noted that they would note conditions of use, transferring procedures in the plant (i.e. piped, open containers), or how workers themselves would use the chemicals. The discussion was much more around risk vs. hazard. One member noted that you could distinguish the potential for exposure for a substance always used in a closed system vs. one that is always used in a batch/bench process. Mike noted that when they developed their thinking around delisting petitions, the chemicals had to be relatively non- toxic to even be brought forward. Expert judgment is based on the discussions of issues, which included; is it used widely in MA, are workers working in open systems vs. closed systems?

One member noted that nPB was a classic example of this in that the potential for exposure is very high – particularly as there are many people with high school education working in drycleaners, etc… Specifically there is no way one could argue under all circumstances the chemical would be in a closed system with no potential for exposure to the worker. Hazard and very high potential for exposure suggest more grounds to keep listed vs. high hazard with minimum potential for exposure.

One member suggested systematizing the procedure for analyzing chemicals, which acknowledges the potential for exposure. Since professional experience in judgment varies, this could capture information in the case that no one is familiar with the manufacturing practices of a particular chemical. Another member noted that if this were considered a checklist item the Board could bring in someone who is knowledgeable in the event the process is outside of the expertise of the Board. It was noted that it is important to look at the whole spectrum of chronic health effects which is more likely to be much more significant for the human species rather than get caught in the scenario that a carcinogen is automatically worse than a systemic toxin, reproductive toxin, etc. Specifically looking at newly designed chemicals– we need to be proactive and step back and look at a hierarchy of criteria. We have to look at both acute and chronic effects. Consider those criteria to be looked at first, then secondary, all things equal what would they move to next.

It was noted that a lot has been learned in the past 15 years. Persistence is much more important looking back. It is a good time to look at thought process and decision criteria – what things are more critical for species, etc.

One member noted that the document needs to be really clearly defined to avoid confusion and/or sidetracking. A comment for inclusion in the guidelines; how it is implemented when not all the same info is known for the chemicals to be evaluated. A member responded that a hierarchy lends itself to that…i.e. how do you proceed with the most critical thing missing, etc. Some chemicals everyone knows are toxic – even though there is no data. It was reiterated that the hierarchy is a GUIDE. It is decision criteria – it isn’t an algorithm for generating an answer. A member noted that they value the use of the DELPHI method in the group and wants to make sure that it is still central regardless of the adjustments.

A benefit could include - a new chemical is missing data on mutagen or reproductive toxicant – yet has a structure similar to known reproductive toxicant – that would be part of the protocol. The similarity in structure could provide a basis for discussion. It was noted that you could be missing reproductive data and the structure doesn’t match anything but still could make a wrong decision. It is less likely for that to be the case.

Ann Marie and Heather will work on a draft for the 22nd. Criteria will be considered first, then wording second. Work can be done offline to tailor the wording, particularly in regard to use. Heather noted she will work on a first draft of the re-write with thoughts from Larry and Ann-Marie. She will look at updating the criteria and hopes to have a draft for the July 22 meeting. Ann-Marie is willing to take a first cut at designing a hierarchy and putting it to a discussion, (she will get it to Heather before the meeting for circulation). This is a particularly good time for the SAB to focus on the document and have it be comprehensive and clear. Heather got consensus that people were interested in the hierarchal process.

Next meeting: July 21

Adjourn