All posts by Ralph Stuart


Chemicals – The Good, Bad, and the Ugly S.B. Sigmann

Public Perception of the Chemical Enterprise The Good The Bad and the Uncertain. M.E. Jones

ACS role in Communicating chemical safety. J. Kemsley

Developing design principles for ‘lesson learned’ laboratory safety videos. H. Weizman

It’s no accident that many journalists don’t write clearly about lab safety incidents. B. Benderly

Hazmat event reporting in the media. R. Stuart

Risk Communication for the Chemist and Non-Chemist. R. Izzo

Emerging Trends in Research Operations

Emerging Energy Saving Technologies for Laboratories. J. Blount

Safe Application of Filtered Fume Hoods. K. Crooks

iLab operating software materials management. C. Lopes

VOC levels in Solvent Cabinets
A.E. Norton, K. Brown, W.B. Connick, A. Doepke, F. Nourain

Convergence of Research Operations and Safety: A mutually bene cial partnership K. Heard

The Role of the EHS Professional in Laboratory Design M.B. Koza

Taking safety management to the next level: Moving from assumptions to reality. S. Schwartz-Hinds, N. Watson

Designing and operating facilities to support the safe conduct of research activities. J.M. Pickel, K.B. Jeskie

Pharmaceutical industry best practices in lessons learned R.A. Sayle, J.W. May

Personal chemical exposure sensor with indoor positioning and robotics for laboratory safety. K. Brown, A. Brandes, A.E. Norton, P.B. Shaw, D.T. Neu, R. Voorhees

Hydrogen gas lab servers provide many advantages to laboratory operations. J. Speranza

Achieving a Balance Between Expansion and Cost Control – Yale University West Campus Research Operations. C.D. Incarvito

DCHAS Awards and Soft Skills Symposium

Division of Chemical Health & Safety Awards

Making Safety Habits By Finding Your Cues, Routines, and Rewards for Safety  R.H. Hill

The State of the Arts Chemical Safety. M. Rossol

Stanford Safety Culture L.M. Gibbs, R. Furr, M. Dougherty

Soft Skills and Chemical Safety

Be Prepared – Things to do before EHS interactions with lab R.M. Izzo

Leveraging Soft Skills. K. Angjelo

Developing and Maintaining Relationships with Research B.S. Chance

Supporting development of chemical risk assessment skills R. Stuart

JCHAS Spotlight: Literature Review – Remediation of Meth Labs

The Editor’s Spotlight for the September / October 2017 issue of the Journal of Chemical Health and Safety is shining on:

Remediation of manufactured methamphetamine in clandestine laboratories: A Literature Review

By Clyde V. Owens

The abstract is:

The purpose of the current literature review was to identify, collect, review, and organize all available information concerning clandestine laboratories used to produce methamphetamine through an analysis of routinely collected data sources. There were numerous peer reviewed journals, electronic databases, websites, and commercial vendors relevant to the remediation process of methamphetamine laboratories. Our intention in this review was to produce background information as well as a reference guide relating to the critical problem of methamphetamine production nationally and internationally in addition to generat- ing future research projects associated with the topic. This literature review determined there has not been a national standardized analytical method recognized as a reference guideline for the remediation of clandestine laboratories for production of methamphetamine.

Other articles in this issue are:

A new language
Harry J. Elston

The efficacy of alkalized liquid hydrogen peroxide for the remediation of manufactured methamphetamine in clandestine laboratories Original Research Article
Clyde V. Owens

Accumulation and risk assessment of heavy metal contents in school playgrounds in Port Harcourt Metropolis, Rivers State, Nigeria Original Research Article
Chioma Joy Okereke, Peter Uchenna Amadi

Development and psychometric evaluation of the Research Laboratory Safe Behavior Survey (RLSBS) Original Research Article
Eric F. Jorgensen

Addressing as low as reasonably achievable (ALARA) issues: Investigation of worker collective external and extremity dose data
Original Research Article
Michael E. Cournoyer, Stephen A. Costigan, Stephen B. Schreiber

Working Safely at the Frontiers of Science

Dr. Glenn Seaborg reflects on plutonium, lab safety, and DivCHAS

May/June 1998

Glenn T. Seaborg, world-renown radiochemist, co-discovered plutonium and nine other transuranium elements. While working on the Manhattan Project, he devised a method of extracting and purifying plutonium. In 1944, his “actinide concept” of heavy element electronic structure changed the periodic table to include the transition series of transuranium elements. Dr. Seaborg shared the 1951 Nobel Prize in chemistry for his work with the new elements.

In 1947, President Harry Truman appointed Dr. Seaborg to the newly established Atomic Energy Commission. Dr. Seaborg continued his public service work as an advisor to the next six administrations and, under President Ronald Reagan, as a member of the National Commission on Excellence in Education. Dr. Seaborg has served as president of the American Chemical Society (1976) and the American Association for the Advancement of Science (1973). Today, he works to further a national commitment to basic scientific research and the safe management of nuclear materials. Editor Carl Gottschall spoke with Dr. Seaborg about the challenges of working safely in a brand new field of chemistry.

Gottschall: Why did you become a chemist?

Seaborg: I was inspired by a high school teacher. I had taken no science in grammar schools or the first two year of high school – my freshman and sophomore years – because I didn’t really have any background that sent me in that direction.

In my junior year, it was pointed out that if I didn’t have a laboratory course in science, I wouldn’t be eligible for admission to the tuition-free state university, which was UCLA. So I took chemistry.

I went to a small high school in the Watts neighborhood of Los Angeles, where I was bused in because we did not have a high school where I was living. My high school chemistry teacher just turned me on to chemistry. His name was Dwight Logan Reid. He not only taught chemistry, he preached it. He told us about the controversies that were raging and the personalities in chemistry. He had us on the edge of our seats.

Then, in my senior year, I had the same teacher. It was a small high school, and they alternated between teaching chemistry and physics. I liked physics even better. But in those day (I graduated from high school in 1929(, there didn’t seem to be any outlets of good chances for employment for a physicist, so I majored in chemistry at UCLA and, of course, at Berkeley, where I got my PhD I took as much physics as I did chemistry. I did my PhD research at Berkeley in nuclear physics but got a PhD in chemistry.

Gottschall: That certainly would help explain why you did so well in radiochemistry, which is a combination of physics and chemistry.

Seaborg: I did most of my research on the borderline between physics bad chemistry.

Gottschall: Perhaps that boundary was too arbitrarily assigned. As I recall, you were instrumental in the formation of the ACS Division of Chemical Health and Safety.

Seaborg: Yes, I reviewed my journals on that. I can tell you how it came about. The proposal for a new division came to a climax at the meeting of the American Chemical Society in Washington, DC in September, 1979. It was announced that the Committee on Divisional Activities opposed the elevation of the provisional Chemical Health and Safety to full division status. They opposed it on some kind of a formality – that it hadn’t met the reporting requirements or something like that.

I attended a meeting of what was called the Science Commission at that time. I knew Howard Fawcett then. He had convinced me of the importance of the Chemical Health and Safety Group becoming a full division. I advocated strongly at the meeting of the Science Commission that this be done. This was actually on September 12 (the first meeting with the Science Commission was on September 11). On September 12, I also attended the meeting of the ACS Council. In that meeting, the chair of the Committee on Divisional Activities, Barbara Montague, recommended rejection of divisional status for the Chemical Health and Safety Group.

Then, at my urging, Chair Warren Falcones of the Science Commission moved that the group be given divisional status, and carried by a voice vote in the Council meeting despite the earlier recommendation of the chair of the Committee on Divisional Activities that the motion for the recommendation for divisional status be rejected.

Gottschall: It has been recognized for years that the division owes quite a lot to your advocacy as well as your eloquence in persuading the Council. That’s not always an easy task. Even now, with so much emphasis on chemical health and safety is only a small fraction of ACSs overall membership. Do you have any ideas on what the ACS should be doing to stress the importance of chemical health and safety?

Seaborg: Perhaps articles like this might give publicity to it.

Gottschall: Perhaps-your eloquence will carry the day again.

Seaborg: I hope so, yes.

Gottschall: As a pioneer in radio-chemistry, you were very well aware of the importance of health and safety evaluations and precautions. How did you handle the same aspects of working with a new element – plutonium

Seaborg: I can give you some history there. I was at the wartime Metallurgical Laboratory at the Manhattan Project of the Plutonium Project Part of the Manhattan Distract at the University of Chicago.

When the first ponderable, visible, weighable amounts of plutonium came into the laboratory from the power plant at Oak Ridge in January, 1944, it suddenly occurred to me that the radiation-monitoring people, I guess you might call them the health physicists, hadn’t given an any attention to the danger from alpha-particle emitters like plutonium. All of the precautions and protections that they had devised were for gamma radiation; you know lead shields, for example.

In view of the problems that had occurred in the late teens and early 1920’s with the radium dial painters, I realized that the ingestion of just a little bit of plutonium would be a greater danger that then radiation from gamma emitters.

So I got in touch with the medical authorities and called the danger to their attention. The led, over a period of a couple of months, to a recognition of the problem and a renovation of the entire laboratory to include additional hood space and air monitoring.

The renovation also included putting linoleum on the floors and covering the walls with shellac that that would could be easily washed down. In general there arose a whole new regime of care in working with the radioactive substances.

The result of these precautions in spite of the fact that we handled plutonium in increasing amounts was that in the ensuing months of 1944 and 1945, nobody in my section suffered from plutonium poisoning. (I was leader of what called Chemistry Section C-1, which at its peak had about 100 scientists, BSs and PhDs.)

Gottschall: The is truly remarkable when you see all of the elaborate glove boxes and –

Seaborg: We developed the glove boxes

Gottschall: I think that is a super example of chemical health and safety at work, although perhaps we should give physical a little bit of credit there also.

Seaborg: Yes, I think so.

Gottschall: What incident or situation involving you personally do you feel was the most potentially hazardous to your health? Potentially, since obviously you are in good health.

Seaborg: It would have been hazardous for me to go into the laboratory if there if they had plutonium in solution; you know, they were stirring with stirring rods and having floating around in the air and so forth. I would say that was probably the most potentially hazardous situation, when we began to have plutonium in visible, ponderable amounts.

Gottschall: Did you wear respirators then?

Seaborg: Yes, in some cases we did.

Gottschall: Plutonium has been called the ‘most hazardous’ or dangerous chemical element, mostly by uneducated people, but also by a few scientists.

Seaborg: These people have it completely wrong. I don’t know how that reputation for plutonium has come about. I guess in an attempt to protect people, they have gone overboard on this. There are many poisons and toxins that are more hazardous than plutonium by far. I have met a number of people who ingested plutonium in what is considered greater than the tolerable amounts 50 years ago, and they are still alive. So, I think that this is a great exaggeration.

Gottschall: I agree. I recently read the paper by Voelz et al. concerning the Manhattan Project people that Los Alamos has been studying for 50 years*. They are very normal, albeit a bit longer lived than the regular population.

Seaborg; That’s right. They are a bit longer lived.

Gottschall: And yet, you were working with new elements that had unknown but potentially harmful properties. You devised methods to work safely with and purify their compounds without the experience or knowledge to confidently anticipate the health hazards. The safety measures you took really made a difference.

* Editor’s note: Voelz, G.L.; Lawrence, J.N.; Johnson, E. R. ‘Fifty Years of Plutonium Exposure to the Manhattan Project Plutonium Workers: An Update.’ Health Physics 1997, 73, 611-619.

Dr. Seaborg’s guidelines for handling plutonium

Concerned about the possibility of hazardous accumulation of plutonium in the laboratory, Dr. Seaborg insisted on absolute cleanliness and proposed seven steps to prepare in the laboratories:

  1. Put linoleum on all floors.
  2. Paint or varnish walls and ceilings.
  3. Remove steam coils from windows and seal all windows
  4. Provide a cleaning crew to mop every hall, office and laboratory and wipe down every laboratory bench, shelf and hood, twice a day.
  5. No laboratory unit should have more than four workers.
  6. Every effort should be made to develop adequate methods for monitoring the air and the equipment in the labs.
  7. Such dangerous practices as eating in the labs must be stopped.

Reference: Seaborg, G.. Plutonium Story: The Journals of Professor Glenn T. Seaborg 1939-1946. Kathren, R: Gough JB; Benefiel GT; Eds: Battelle Press, Columbus, OH 1994 p.411

Wednesday, January 5
Journal Entry, Glenn Seaborg, Wednesday, January 5, 1944

As I was making the rounds of the laboratory rooms this morning, I was suddenly struck by a disturbing vision. I pictured in my mind the expanding scale of work with solutions containing plutonium that will soon result from the large quantities of plutonium to be received from Clinton Laboratories. I visualized beakers of plutonium solution throughout the laboratory rooms, and it struck me forcibly for the first time that plutonium handling will no longer be confined to microquantities manipulated by specially trained experts. Recalling the health problems incurred by workers in the radium dial painting industry, I realized clearly that similar hazards face those of us working with alpha-particle-emitting plutonium-239.

I was struck by the fact that despite the great care in planning by the Project medical people, no one has anticipated and made specific provisions for the wide-scale handling of alpha-active material, which presented special hazards of ingestion. It became clear to me that our rather ordinary laboratory hoods are inadequate for this task and that rather extensive rebuilding of our laboratory facilities to emphasize adequate air flow and extraordinarily clean operations will be necessary. I am determined that none of the people for whom I am responsible shall be subjected to any avoidable dangers from handling alpha-active plutonium. I immediately returned to my office and sent the following to Dr. Stone:

“It has occurred to me that the physiological hazards of working with plutonium and its compounds may be very great. Due to its alpha radiation and long life, it may be that the permanent location on the body of even very small amounts, say one milligram or less, may be very harmful. The ingestion of such extraordinarily small amounts as some few tens of micrograms might be unpleasant if it located itself in a permanent position. In handling the relatively large amounts, soon to begin here and at Site Y, there are many conceivable methods by which amounts of this order might be taken in unless the greatest care is exercised.

“In addition to helping to set up safety measures in handling so as to prevent the occurrence of such accidents, I would like to suggest that a program to trace the course of plutonium in the body be initiated as soon as possible. In my opinion, such a program should have the very highest priority.”

Timeline of Dr. Glenn T. Seaborg

1934 B.S. University of California, Los Angeles
1937 Ph D University of California – Berkeley; joined chemistry faculty at Berkeley
1940 Began collaboration with E M McMillian, isolated plutonium (element 94)
1941 Isolated uranium-233; established thorium’s nuclear fuel potential
1944 Identified americium (element 95) and curium (element 96)
1944 Plutonium safety manual
1945 Professor of chemistry, University of California, Berkeley
1949 Identified berkelium (element 97)
1950 Identified californium (element 98)
1951 Shared Nobel Prize with EM McMillian for discovery of elements
1952 Identified einsteinium (element 99)
1953 Identified fermium (element 100)
1955 Identified mendelevium (element 101)
1958 Identified nobelium (element 102)
1958-1961 Chancellor of the University of California – Berkeley
1961-1971 Chairman, US American Energy commission
1973 President of the American Association for the Advancement of Science (AAAS)
1974 Identified seaborgium (element 106)
1976 President of ACS
1979 Chemical Health and Safety given full status at ACS
1982-1984 Director, Hall of Science, University of California – Berkeley
1984 Chairman, Lawrence Hall of Science
1994 Element 106 named seaborgium at the 207th ACS National Meeting

JCHAS Spotlight: Ergonomics of Glove Boxes

The Editor’s Spotlight for the July / August 2017 issue of the Journal of Chemical Health and Safety is shining on:

Rotator cuff strength balance in glovebox workers (link to PDF version)

By Cindy M. Lawton, Amelia M. Weaver, Martha K.Y. Chan, Michael E. Cournoyer

The abstract is:

Gloveboxes are essential to the pharmaceutical, semi-conductor, nuclear, and biochemical industries. While gloveboxes serve as effective containment systems, they are often difficult to work in and present a number of ergonomic hazards. One such hazard is injury to the rotator cuff, a group of tendons and muscles in the shoulder, connecting the upper arm to the shoulder blade. Rotator cuff integrity is critical to shoulder health. This study compared the rotator cuff muscle strength ratios of glovebox workers to the healthy norm. Descriptive statistics were collected using a short questionnaire. Handheld dynamometry was used to quantify the ratio of forces produced for shoulder internal and external rotation. Results showed this population to have shoulder strength ratios significantly different from the healthy norm. Strength ratios were found to be a sound predictor of symptom incidence. The deviation from the normal ratio demonstrates the need for solutions designed to reduce the workload on the rotator cuff musculature in order to improve health and safety. Assessment of strength ratios can be used to screen for risk of symptom development. This increases technical knowledge and augments operational safety.

Other articles in this issue are:

Whither CSB?
Harry J. Elston

A software for managing chemical processes in a multi-user laboratory
F.E. Camino

Rotator cuff strength balance in glovebox workers
Cindy M. Lawton, Amelia M. Weaver, Martha K.Y. Chan, Michael E. Cournoyer

Assessment of shooter’s task-based exposure to airborne lead and acidic gas at indoor and outdoor ranges
Jun Wang, Hailong Li, Marcio L.S. Bezerra

Make safety awareness a priority: Use a login software in your research facility
F.E. Camino

Webinar Questions: Risk and Green Chemistry Rating Systems

There were 12 questions about risk and green chemistry rating systems raised by the audience.

These answers are from both Dr, Denlinger and Mr. Stuart; feel free to share your thoughts and follow up questions in the comments section below. (Note: the comments section is moderated, so there may be some time delay before your question shows up.)

1.) Who decides these risk and consequence coefficients – are they in any way standardized?

Kendra’s response: The individual filling out the JHA decides which numbers should go into the risk rating calculation. I think it would be possible to standardize them in some ways (see question 7), but in the end there will always be some differences from one researcher to another.  

Ralph’s additional comment: In an ideal world, we would be able to use statistical analysis of real world incidents to assign these coefficients; however,  adverse lab incidents are not well documented, so such data is not readily available in most cases, particularly in the research setting. For this reason, ultimately, these coefficients will represent human judgements.

However, the goal of the process is to prioritize the hazards of the process so that control measures can be appropriately applied to those hazards. Fortunately, this prioritization can usefully proceed without statistical evidence, by enlisting a qualified team of people to perform the JHA based on their experience with similar processes. 

2.) The JHA shown missed stating the physical electrical hazards.

Kendra’s response: Good point!

Ralph’s additional comment: This is a good example of how safety reviews can benefit from reviews by other people.

3.) Is there any way to scale the green lab and risk assessment process up so that we are evaluating labs or specific projects or students.  Researchers may find the time required to evaluate each reactions prohibitive. 

Kendra’s response: Yes, there probably would be many ways to scale up the risk assessment process in order to save time. However, I would caution against doing so. I found it so interesting and helpful because of the individual nature of the JHA and the fact that it takes some time to fill out completely.

In my experience, too many students are thrown into the lab setting with little training to perform their duties safely, and requiring the JHA before performing something new in the lab would help alleviate this problem because the student is forced to sit down and actually think about what they’re going to do. Furthermore, it seems to me that safety should be a focus of the graduate school experience, so the time spent filling out JHA’s could become part of the process of obtaining a PhD rather than something extra.

Ralph’s additional comments: In the environmental health and safety world, this strategy is called “hazard banding” or “control banding“, depending on the specific application. As you suggest, this approach is driven by resource constraints, so it requires omitting process specific information from the hazard management process. So I agree with Kendra that this approach has to be carefully managed in the academic setting.

In that context, I would like to add that my experience is that safety review of chemical processes become quicker over time, particularly in the context of a specific research program. However, as Kendra suggests,  in the academic research laboratory, focused on the student experience, JHA’s for individual processes are appropriate, as they avoid the “Chinese whispers” or “telephone” problem associated with the oral transmission of process safety knowledge. As Dwight Eisenhower (among others) said: Plans are worthless, but planning is everything. This means to me that the JHA discussion is the point of the exercise, rather than the completed form.

4.) I would encourage you to incorporate a few basic biological parameters into your safety protocols.

Ralph’s response: If you are referring to managing biological hazards used as part of the research process, these are well addressed by Biosafety in Microbiological and Biomedical Laboratories, 5th Edition

5.) How much time does it take for hazard assessment in an organic chem research lab, and What time line do you recommend?  

Kendra’s response: It took me about an hour to fill out my JHA, though it was for an experiment that I’ve performed many times. It would probably take a bit longer for something new, AND it would be important to discuss the experiment with anyone in the lab who has performed it before or used the same chemicals and experimental set-up.

6.) Can this tool be used to define low risk labs and help keep them that way for ventilation savings? 

Kendra’s response: That’s a really interesting question! It seems like it could definitely be adapted for that purpose, though there would need to be some guidelines in place to make sure nothing changes (like ordering a new chemical that is more hazardous than those used in the past).

Ralph’s response: This is an approach that is of great interest to many people.  While at Cornell University, I helped to write an Laboratory Ventilation Management Plan that uses this strategy. In addition, I have published several articles in the Journal of Chemical Health and Safety that describes this approach in the LVMP.

7.) How do you quantify your hazard rating and quantify the probability of occurrence during the hazard analysis? Would each individual have the same risk level or will that vary significantly researcher to researcher? 

Kendra’s response: I assigned risk ratings using my experience in the lab. Newer students would probably need to get help from more senior students or research advisers. It’s also possible their risk ratings would be different because they’re newer to conducting research—they might be more likely to spill a chemical, for example. In this way, JHA’s might vary for one researcher as he or she gains more experience working in the lab.

The risk ratings would probably vary quite a bit from researcher to researcher, though the JHA is meant to be completed and used on more of an individual basis than some of the other hazard assessment tools. It seems like it would be possible to add in some guidelines to aid in conformity, like using SDS terms to correspond to severity of consequences (harmful, toxic, fatal).

Ralph’s comments: My experience has been that variations between researchers occurs when they are making different assumptions about a process. For example, some people might have easy access to a fume hood to perform their chemical work in, while others may not.  This difference can greatly impact the risk ratings and the consequent JHA. Identifying these differences are a key advantage of reviewing the JHA with other chemists.

8.) Has the safety of nano materials been addressed in this type of safety concerns?

Ralph’s comment: Yes, NIOSH, among others, has been conducting significant research into the hazards of nanomaterials. See their Nanotechnology web page for more information on this.

9.) Has an Life Cycle Assessment been conducted on the overall environmental and safety impacts of solvent use vs the alternative reaction methodologies? 

Kendra’s response: I’m not aware of any studies like this.

Ralph’s comment: I suspect that the ACS Green Chemistry institute web site would good place to look for such a LCA.

10.) Green solvent: I think there is exaggeration in using the word green in chemistry, especially solvents used for chromatography. Except for water, I don’t think there is any reagent that one can call “green”. Any thoughts? Thanks a lot 

Kendra’s response: We can really only talk about green chemistry when comparing more than one thing—solvent, reagent, process, etc. There are some cases where using water might be worse than using something else due to the disposal and treatment process. We can’t just look at something and decide that it’s green; we have to have something with which to compare. Toluene isn’t something you might label as being green, but most chemists would agree that it’s greener than using benzene. Even making that small change is better than doing nothing.

11.) Does the ecoscale assign a penalty for fairly benign solvents like water? 

Kendra’s response: No penalty is assigned for the use of water. As far as other solvents go, you can try it yourself using their online calculator! Find it here.

12.) A risk rating of 80 is clearly bad, but does the Hazard Assessment Tool help one evaluate a process involving five RR=10 tasks vs an alternative process involving twenty RR=5 tasks?

Kendra’s response: In and of itself, the JHA does not necessarily help compare a process with an alternative one. Green chemistry metrics can be helpful for comparing two different processes, though there will probably be certain aspects of one that are better and certain aspects of the other that are better.

In some cases, the user’s chemical intuition is the best tool to help decide which route to take after these comparisons have been done. I would probably want to avoid using a particularly hazardous chemical (where severity of consequences would be life-threatening, for example), even if it meant doing 2 or 3 extra steps that were lower risk. In the end, though, it’s going to come down to the individual chemist; the JHA is used to make sure that person knows the risks exist, but it’s up to the individual chemist to decide what to do with that information.

Ralph’s comment: As I suggested above, the research laboratory’s available equipment  and resources will impact  the best strategy for managing chemical hazards, so the ACS tool does not try to address all situations. Rather, it outlines best practices for addressing the issues raised by the Chemical Safety Board’s report on academic laboratory safety.


Webinar Questions: Green Chemistry Techniques

There were 14 Green Chemistry technique questions raised by the audience.

These answers are Dr. Denlinger’s; feel free to share your thoughts and follow up questions in the comments section below. (Note: the comments section is moderated, so there may be some time delay before your question shows up.)

1.) What safety practice is applied when opening the Ball Mill vials after the reaction? 
After taking the vial out of the ball mill, it is usually clamped in a vise and the cap is removed using a wrench. This is also done under a snorkel, since in some cases gas or vapor escapes when the vial is opened.
2.) What is the largest scale at which you have run a ball milled reaction? 
The largest scale I’ve personally run one of my reactions produced 500 mg of my desired product. Our standard stainless steel vials are about 3.5 mL in volume, and our large stainless steel vials are about 64 mL in volume.
3.) What are the limitations or downfalls to ball-milling?
It would be difficult to perform a reaction that required a gas as a reagent, since we rely on the motion of the ball to grind our reagents together during ball milling (though there are also advantages to this: see “Conducting moisture sensitive reactions under mechanochemical conditions”). Creative solutions might be found, though, such as using dry ice as a CO2 source (see “The solvent-free and catalyst-free conversion of an aziridine to an oxazolidinone using only carbon dioxide”). We have also tried reactions that occur through radical mechanisms and have not had any success with those yet.
4.) What about oxidizers?
One of my projects is the oxidation of alcohols under ball milling conditions, and several oxidizing agents were tested (ex. TEMPO, Oxone®, mCPBA). No accidents have ever occurred, and nothing was out of the ordinary with these reactions as compared with others that did not involve oxidizing agents.
5.) I assume based on reactivity arguments that there are some reactions that may not be amenable to solvent-free solid state reactions.  Have you encountered such situations (reactions that went out of control, etc.)? 
We haven’t encountered any reactions that went out of control in our system. For the most part, the research process is the same for us as any other organic chemists. We try something, and if it doesn’t work at all or we observe low conversion to product, we change the system and try again. There are certainly reagents that we would not put into a ball mill, but in those cases we look for safer alternatives that can carry out the same transformation (using Cs2CO3 as the base for the Wittig reaction instead of n-BuLi is one example).
6.) I am using THF for GPC, how can I change that to a GC solvent? 
The simplest change you can make is to switch to 2-methyl-THF, but there are some other options available if that wouldn’t work for you (see “Updating and further expanding GSK’s solvent sustainability guide “ for examples).

7.) How easy to separate solid solid compared to liquid liquid in terms of green chemistry?
We still use solvent to extract our reaction mixtures from our vials, so for separations it’s a matter of choosing a solvent that will dissolve the product. Solvent selection guides can be used to help make the greenest choice possible for separations, especially if chromatography has to be used. I’m working on my project with polymer resins so that we can green up the separation process as much as possible. Avoiding solvent for the reaction phase of the process still helps prevent waste, but we also want to expand that philosophy as much as we can to the isolation/purification process.

8.) How difficult is material removal from the Ball Mill vials?  Does it require any liquid aids?
Removal of material from the ball mill vials is not that difficult as long as an appropriate solvent is chosen (see question 7). Yes, we do use solvent to aid the removal of material from the vials and subsequent isolation (whether it’s gravity filtration, liquid-liquid extraction, or chromatography).

9.) Has anyone assessed particle exposure around the ball-milling set-up?

No, but that might be a good thing to analyze just to make sure we have the safest set-up possible. We usually tighten the caps onto the vials with a wrench to ensure no reactants leak out, but it is possible to smell highly volatile reagents while they are being ball milled. That definitely indicates that vapor at least is able to escape, so very small particles might be able to escape as well.

10.) Ball-milling – I have heard of but never tried it – is it truely a solid-solid reaction or is it more like a melt where under heat/friction you get a liquid phase?
Our indirect evidence suggests that our reagents react with each other whether or not they melt under our conditions. Using an iButton to measure the temperature of the vial during the reaction indicates that the vial reaches a temperature of about 45°C. So any reagents with melting points lower than that are probably melting, but anything with a melting point higher than that probably is remaining as a solid.

11.) Are the polymer resins you’re using recyclable? 
Yes! For the Wittig reaction, we don’t reuse the polymer because it has changed from triphenylphosphine to triphenylphosphine oxide. For some of my other projects, however, a catalyst is attached to the polymer. This catalyst is not used up or changed during the reaction, so I can scrape it off the filter paper after gravity filtration, save it, and use it again. In one project it is possible to use the same polymer-bound catalyst sample at least 5 times with no change in its activity.

12.) Are the ball mills safe when dealing with crystal morphologies and materials that could decompose explosively (shock)?
I have not used any reagents that would fall into that category, and in general we try to find alternative routes in order to avoid specifically hazardous chemicals. There is one example of using azides under ball milling conditions (see “Scratching the catalytic surface of mechanochemistry: a multi-component CuAAC reaction using a copper reaction vial”), and no safety issues arose.

13.) A sequestering solid support will not have much resolving power for separating related components so it has limited utility BUT more importantly a lot of solvent goes in to making these resins so it is questionable how green they are – have you done such an analysis?
These solid-supported reagents are tools in the green chemistry toolbox—they cannot be applied in every chemical process, but there are certainly many processes that would benefit from them. In cases where a reaction or process would not benefit from a re-design using solid-supported reagents, other tools in the green chemistry toolbox could be applied. This might consist of choosing safer solvents, choosing different reagents, using photochemistry or microwave chemistry, or any of the myriad ideas published in journals such as Green Chemistry and ACS Sustainable. The fact that we cannot fix everything immediately does not mean that we shouldn’t try to fix what we can. Even making a small change to be safer or greener is better than what we were doing before, and making many of these small changes can result in a big change overall.

Not only is solvent used to make these resins, but many other reagents that may or may not be particularly safe are used as well. My work on the Wittig reaction was an extension of a proof-of-principle project to understand how these solid-supported reagents behave under ball milling conditions. In order to address the problem you mentioned, I also investigated the possibility of using ball milling to functionalize a polymer itself. This would give us more control over the greenness of the functionalization process. Furthermore, I investigated using a polysaccharide backbone instead of polystyrene, so that the solid support employed would be biodegradable and derived from renewable resources. We plan to publish that work this summer.

14.) what amount (mass) of reagents are used in ball mills?
The amount used can vary from one ball milling group to another, but in our group we usually try to work on the 1 mmol scale (so producing about 100-200 mg of product, depending of course on the specific compound). We can vary that number a bit, but we are constrained to the approximately 3.5 mL volume of the regularly used stainless steel vials.