Category Archives: May 2017 Webinar Follow Up

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.


Webinar Questions: General Lab Safety

There were 9 general lab safety topics raised by the audience.

These answers are Ralph Stuart’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.)

Can you talk more about the safety & health issues in the laboratory? Specifically, what are the general policies for the hazards of broken glassware and dealing with students cut by broken glassware?

General laboratory safety issues, as well as glassware specifically are well covered by the ACS publication Safety in the Academic Laboratory. A reminder: Remember to check with the host institution for its protocols related to providing first aid before lab work starts, as glass cuts are one of the most common laboratory injuries.

How do I access or subscribe to the Journal of Chemical Health and Safety?

The Journal of Chemical Health and Safety (this link will take you to the Journal’s web site) is a member benefit of the Division of Chemical Health and Safety and is also available in many academic libraries. 

I am most concerned about the Risks (vs Hazard) within chemical reactions.

This is an important point. The risks associated with a chemical reaction are often not clear from a review of the Safety Data Sheets for individual chemicals, so further safety analysis of the process as a whole is necessary. This issue was identified by the Chemical Safety Board’s 2011 report and the ACS is working hard to support this process with the technical resources outlined in the webinar.

Two related questions:

  • Another thought is treating students like workers and getting them OSHA protection – never saw this in my time in academia, but in industry, I got a benign chemical splash between glove and coat and the reporting on that went on for 12 months and involved a lot of discussion and meetings around chemical practices
  • In 2003, U. Iowa Dept. Chemistry had an explosion from one of the grad students running a solvent still, where he was burned (3rd degree) and hospitalized.  There was a lot of controversy afterwards, because the university did not intend to cover medical bills, stating that student insurance did not cover graduate teaching assistants that were involved in lab research (only graduate research assistants were covered).  Eventually the student union became involved and this was resolved.  However, does this continue to be an issue in academia?  With respect to hazards for graduate/undergraduate research, has there been any legislation to cover students injured in an accident by workers comp/disability?

The academic laboratory is an interesting challenge in this respect. Traditionally, higher education has been what the former head of OSHA, among others, has referred to as a “fissured workplace”. This phrase describes workplaces in which employees and students work together under a wide variety of institutional relationships (e.g. full time employees, visiting scholars, tuition-paying students, volunteers, etc.). This situation presents an interesting challenge to developing and sustaining an active laboratory safety culture because the legal requirements applicable to each group will vary depending on their status and the legal jurisdiction that applies.

Do you follow OSHA 1910. 1450 requirements?

This question refers to the OSHA Lab Standard found here. This question is answered on an institution-by-institution basis. We have a Chemical Hygiene Plan at Keene State and the University of Cincinnati.

How do you apply process safety management principles in the research lab environment?

This issue is well explored by a 2009 article in the Journal of Chemical Health and Safety by Neal Langerman entitled Lab-scale process safety management. Dr. Langerman expanded on this article in a 2015 JCHAS column entitled Expand Process Safety Management

Can you explain Control Banding, and how effective it is?

Control banding is an area of active research in laboratory safety profession. The concept is to address control of laboratory hazards for a group of chemicals, rather than a process-by-process basis, in a more general way than allowed by tools such as a Job Hazard Analysis. However, control banding is complicated by the variety of physical and health hazards associated with chemical processes used in the research setting. To be effective and sustainable, an ANSI Z10 style Management System should be developed to support the control banding process.

Can we design our safety assessment checklist or we have to follow yours?

It is best practice for checklists to be as specific as possible to the laboratories that use them. General guidance for the best use of checklists can be found on the ACS hazard assessment web site here.

Any feedback from educators and researchers about the ACS Hazard Assessment webpage and tools?

The tool is still new to the world (it was released on the web in 2016), so Kendra’s case study of its use is one of the earliest we in ACS have found. We are very interested in other feedback on the tool; e-mail to provide your comments.


Q&A on Hazard Assessments webinar

On May 11, 2017, Ralph Stuart and Dr. Kendra Leahy Denlinger presented an ACS webinar on Creating a 21st Century Chemical Research Laboratory: Hazard Assessments and Fundamentals. This webinar was co-sponsored by the DCHAS and the ACS Green Chemistry Institute.  Their slides can be downloaded from the ACS Webinar web site. The primary topic of discussion was the JHA section of the ACS Hazard Assessment web site, but other topics, including ball-milling as an alternative to solvent-based chemistry, Green Chemistry metrics and ACS lab safety resources were covered.

Because of time limits, some of the 50+ questions asked by the audience were not answered, so our response to some of the most common questions are provided here. The questions are organized into 5 categories:

  1. General Lab Safety Issues
  2. Laboratory Safety Culture Questions
  3. Risk and Green Chemistry Rating Methods
  4. Green Chemistry Techniques

Click on the links above to see our responses to the audience’s questions. If you have follow-up questions, feel free to contact Ralph or Kendra by e-mail.

Webinar Questions: Laboratory Safety Culture Questions

There were four related questions and comments relative to Lab Safety Culture. 

  • Who is responsible for chemical safety in the lab? (Everyone is a fine answer, but also a dodge). I feel it starts with the supervisor/mentor and I dislike the way accident blame tends to get pushed towards the victim.
  • University chemistry depts operate funded largely by NIH/NSF/DOE grants. In awarding these grants, there are requirements to follow bio-safety, radiation safety animal welfare, student mentoring guidelines. But chemical safety is left to the local university and fire marshals to regulate. BUT there could be chemical safety requirements IF they could be clearly codified and agreed to. The enforcement comes from losing grant support BUT the key is they have to be clearly defined for what are wide ranging activities and there has to be reporting back to the granting agencies.
  • It would be good to note that Prudent Practices and Safe Science from the National Academies came out of the Board on Chemical Sciences and Technology. They also have a publication on producing Laboratory SOPs. All of them are available for free through the National Academies Press.
  • From my understanding, PIs are primarily responsible for ensuring that researchers who participate in their laboratories receive proper safety training prior to participating in the lab. This coincides with the outcome to the incident that occurred in California when a researcher died due to lack of training.

These comments and questions point to an interesting challenge – the decentralized, entrepreneurial nature of lab work within a larger organization.This issue is the focus of many of the safety culture resources I identified during the webinar, in particular Safe Science from the National Academies Press.  The ACS Hazard Assessment web site outlines the roles and responsibilities related to lab safety here. It is clear from the literature that chemical safety requires both leadership from lab management and empowerment of individual lab workers to be effective and sustainable over time.

What role can lab informatics and Electronic Lab Notebooks play in creating the culture of safety?

This is a very active area of research collaboration between the DCHAS and the ACS Division of Chemical Information. We are using the RAMP paradigm to identify resources and gaps in the electronic lab safety resources available to the laboratory chemist. It is important to note that education for chemists in both laboratory safety and chemical information skills is an important part of a scientific education, both in terms of the sciences of information management and risk management and in practice of these skills while chemistry lab work is being practiced.

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