Chapter 5: Highly Reactive Chemicals

Revised January 2023

General Work Procedures

Highly reactive chemicals include those that have the potential to vigorously polymerize, undergo a vigorous condensation or oxidation-reduction reaction, or become self-reactive due to shock, pressure, temperature, light, or contact with another material. Examples of highly reactive chemicals are explosives, peroxides, water-reactives, and pyrophorics. All work involving highly reactive chemicals should be approved by the laboratory supervisor before initiation of the work.

Handle reactive chemicals with caution, including segregation in storage and prohibition of mixing even small quantities with other chemicals without consideration of appropriate procedures and use of appropriate personal protective equipment.
Chemical reactions conducted at temperatures or pressures above or below ambient conditions must be performed in a manner that minimizes hazards such as explosion or vigorous reaction.
- Provide a mechanism for adequate temperature control and dissipation of excess heat and pressure.
- Use shielding as appropriate to minimize personnel exposure and injury, and facility damage, resulting from over-pressurization or implosion.
Minimize the quantity of reactive chemicals used or synthesized to the smallest amount needed.
- When conducting reactions that involve highly reactive or explosive chemicals, limit the reactants to no more than 0.5 g in the reaction vessel and do not synthesize more than 0.1 g of product in a single run. Exceptions to this must be specifically approved by the laboratory supervisor and appropriate written procedures, training, and mitigation controls must be in place.
Utilize shields and barricades, and personal protective equipment (such as face shields with throat protectors and heavy gloves) whenever there is a possibility of explosion, implosion, or vigorous chemical reaction.
Glass equipment operated under vacuum or pressure must be shielded, wrapped with tape, or otherwise protected from shattering.

Organic Peroxides

As a class, organic peroxides are one of the most hazardous chemicals commonly used in the laboratory. Most organic peroxides are sensitive to heat, impact, friction, light and readily react with oxidizing and reducing compounds, and are highly flammable. Since the sensitivity and instability of these compounds vary, always thoroughly review the properties of specific compounds prior to their use.

Do not use metal spatulas, stirring bars, or other metal items to handle peroxides, as metal contamination can lead to explosive decomposition.
Avoid friction, grinding, and other types of impact near peroxides (especially solid peroxides).
- Do not store organic peroxides in glass containers with screw-cap lids or glass stoppers, use polyethylene containers, screw-cap lids, or stoppers.
After each use, carefully wipe the container neck, cap, and threads with a cloth before resealing.
Clean up all peroxide spills immediately.
Contact the CHO for assistance with the disposal of pure peroxides.

Pyrophoric Chemicals

The Globally Harmonized System (GHS) of classifying and labeling chemicals recently adopted by OSHA defines a chemical as pyrophoric if a small quantity of the chemical will ignite within 5 minutes after coming into contact with air. Of particular concern are liquid or gaseous chemicals which very rapidly (immediately) ignite upon exposure to air as they represent the greatest risk for fire and injury to personnel. Additionally, some chemicals that are classified as water reactive can react with water vapor in ambient air to produce flammable gases, which can ignite. For practical laboratory safety purposes these water reactive chemicals can be grouped with pyrophoric, air-reactive chemicals.

Because of the unique fire risk presented by pyrophoric chemicals, their use requires special handling procedures to avoid contact with air. Laboratories that possess or use pyrophoric chemicals require written SOPs that provide specific guidance on storage, use, and disposal of these chemicals. Additionally, all personnel who handle pyrophoric chemicals must be specifically trained on safe handling procedures and this training must be documented.

Examples of Pyrophoric Chemicals

Grignard Reagents: RMgX (R=alkyl, X=halogen)
Metal alkyls and aryls: Alkyl lithium compounds; tert-butyl lithium
Metal carbonyls: Lithium carbonyl, nickel tetracarbonyl
Metal powders (finely divided): Cobalt, iron, zinc, zirconium
Metal hydrides: Sodium hydride
Nonmetal hydrides: Diethylarsine, diethylphosphine
Non-metal alkyls: R3B, R3P, R3As; tetramethyl silane, tributyl phosphine
Phosphorus
Potassium
Sodium
Gases: Silane, dichlorosilane, diborane, phosphine, arsine)

A more comprehensive listing of pyrophoric chemicals is available in Bretherick’s Handbook of Reactive Chemical Hazards, seventh edition, Vol. 2 (“Pyrophoric Materials), P. G. Urben (Ed.) (2007).

Hazards

The propensity of pyrophoric chemicals to spontaneously ignite on contact with air and/or water represents a high fire risk and requires that they be handled under an inert atmosphere. Strict exclusion of air and/or water requires use of an inert atmosphere glove box and/or special handling techniques. Other hazards may also be associated with pyrophoric chemicals, to include physical hazards such as corrosivity, water reactivity, and formation of peroxides. Pyrophoric chemicals are also generally toxic and health hazards may include liver, kidney, and central nervous system toxicity.

Before Working With Pyrophoric Chemicals

All personnel who handle pyrophoric chemicals must receive documented laboratory-specific training on the chemicals they will use and the procedures that they will perform. Each individual must demonstrate proficiency in handling pyrophoric chemicals and performing the procedures to be conducted, as appropriate for the particular chemical(s) and procedure(s). Conduct of this training and evaluation of personnel proficiency is the responsibility of the PI; however, these tasks can be delegated to a qualified designated alternate.
Review Safety Data Sheets, technical bulletins, and other hazard information to identify and understand hazards and risk mitigation procedures. Sigma-Aldrich Technical Bulletin AL-134, Handling Air-Sensitive Reagents, is a widely used reference that should be reviewed by all personnel who use liquid pyrophoric chemicals. Sigma-Aldrich Technical Bulletin AL-164, Handling Pyrophoric Reagents, should also be reviewed prior to working with liquid pyrophoric chemicals.
Prepare a written SOP that includes procedures for safe storage, use, experimental set up and equipment, disposal, and incident response (fire, etc.) so that associated risks are controlled to a level that is considered to be safe.
Review any proposed changes to laboratory procedures with the PI or other designated knowledgeable person before implementation. Consider the potential for changes to introduce new hazards or increase risks (e.g., scale up of reactions, change of reactants or reaction conditions) and use appropriate methods to mitigate new hazards or increased risks.
Consider performing a “dry run” of new procedures involving pyrophoric chemicals to help identify overlooked handling issues or hazards, and to increase users’ proficiency.

Engineered Controls and Safety Equipment

When available and practical, use an inert atmosphere glove box when handling pyrophoric chemicals.
When an inert atmosphere glove box is not available or practical, handle pyrophoric chemicals in a chemical lab hood. Pyrophoric chemicals are commonly mixed with flammable solvents or used with flammable solvents and a lab hood is necessary to exhaust flammable vapors and reduce the likelihood of fire.
An appropriate fire extinguisher must be readily available in the work area where pyrophoric chemicals are used. An ABC (standard dry powder) extinguisher is required when using pyrophoric chemicals in flammable solvents. A class D extinguisher is required when using solid pyrophoric metals. Do not use a carbon dioxide extinguisher or water to extinguish a fire involving pyrophoric materials since they can enhance the combustion of some pyrophoric materials. If you are expected to use a fire extinguisher to fight a fire you must complete fire extinguisher training annually.
Dry soda lime or sand can be used to cover and extinguish small fires resulting from drips or small spills of pyrophoric chemicals or at ends of syringes used to transfer pyrophoric chemicals. Sand should not be used to extinguish lithium fires but dry graphite can be used.
A working and accessible emergency eye wash and shower must be readily available.

Personal Protective Equipment

Use safety glasses or goggles as appropriate for the chemicals being used and their quantity. Wear a face shield, worn over safety eyewear, whenever there is a risk of explosion or large chemical spray or splash.
Wear chemical resistant gloves appropriate for the pyrophoric chemical, or in the case of a pyrophoric chemical in solvent, gloves that are appropriate for the solvent. For labs that routinely handle pyrophoric chemicals outside of an inert atmosphere glove box, Nomex pilot gloves are strongly recommended where their use does not increase the risk due to reduced dexterity or other factors. If working with a high toxicity chemical that readily absorbs through skin, the proper chemical resistant glove can be worn underneath (gloves made of nitrile material are generally recommended).
Flame resistant lab coats should be worn and ideally be made of Nomex or equivalent fire resistant material. For labs that routinely handle pyrophoric chemicals outside of an inert atmosphere glove box, flame resistant lab coats are required.
Clothing made of synthetic materials should not be worn when handling pyrophoric chemicals.

General Safety Procedures

Never work alone when handling pyrophoric chemicals; always use the buddy system. Whenever possible, avoid working with pyrophoric chemicals outside of normal university business hours when there are few people around to help in the event of an incident.
Limit the quantity of pyrophoric chemicals acquired in order to minimize the quantity that must be stored, and use the smallest quantity needed to accomplish the scientific goal
Before working with pyrophoric chemicals, remove all unneeded and excess chemicals from the lab hood or other immediate work area, especially flammable/combustible chemicals and common combustible materials (e.g., paper).

Handling Pyrophoric Solids

Solid pyrophoric solids are less reactive upon exposure to air than are liquid pyrophoric chemicals; however, safe handling procedures are still required.

Many pyrophoric solids can release flammable or toxic gases; therefore, they should be handled in a lab hood.
Store pyrophoric solids under an inert atmosphere and do not store near heat sources, oxidizers, flammable solvents, or water sources.
Mildly pyrophoric solids such as dispersions of sodium hydride and lithium aluminum hydride in hydrocarbon solvent can be handled in air for short periods of time. The dry, solid forms must be handled under an inert atmosphere.
The reactivity of pyrophoric metals (e.g., aluminum, magnesium, alkali metals) is proportional to their surface area, with finely divided shavings or powder reacting very rapidly with air/water.
Solid pieces of sodium, potassium, and lithium are stored under mineral oil (lithium is also stored under argon) to reduce oxidation to oxides/hydroxides and to reduce pyrophoricity. When stored under oil, these materials should be cut under oil and then transferred to a container with hydrocarbon solvent (e.g., hexane) to rinse off the oil.
Potassium is more reactive than lithium or sodium and during prolonged storage potassium can undergo oxidation to form a potassium superoxide (yellow) coating. Potassium superoxide is shock sensitive and this coating can explode on handling (especially when cutting solid potassium with superoxide coating).

Additional information on general safe handling procedures for solid pyrophoric chemicals is available in the Pacific Northwest National Laboratory documents, Handling Pyrophoric Reagents.

Handling and Transfer of Pyrophoric Liquid Chemicals

When transferring liquid pyrophoric chemicals outside of an inert glove box, a maximum of 50 ml may be transferred using a syringe equipped with a 1 – 2 foot long needle. Transfer of larger quantities should be performed using a cannula technique.
Procedures for handling and transfer of liquid pyrophoric chemicals must be in agreement with currently accepted safe laboratory practices. Published information on handling and syringe and cannula transfer techniques is available in the Sigma-Aldrich Technical Bulletin AL-134, Handling Air-Sensitive Reagents.

Storage

During prolonged storage the integrity of pyrophoric chemicals, especially liquids, can be compromised due to loss of solvent, decomposition, or reaction with trace contaminants. The quantity of pyrophoric chemicals acquired should be limited to quantities that will be used in planned experiments in order to avoid prolonged storage.
Pyrophoric chemicals are best stored in an inert atmosphere glove box. If it is not possible to store pyrophoric chemicals in an inert glove box, store pyrophorics in an air-tight container (under an inert atmosphere) in a flammable storage cabinet dedicated to storage of pyrophoric chemicals. Do not store pyrophoric chemicals together with flammable chemicals in the same flammable cabinet.
Store pyrophoric chemicals in their original manufacturer container (e. g., Sure Seal bottles) unless experimental work requires transfer to other containers. Septum tops may leak after perforation so inspect them on a regular basis and replace as needed (using an inert glove box).
Pyrophoric chemicals that require refrigeration must be stored in a refrigerator that is designed and constructed for storing flammable liquids. Pyrophorics should be stored in a dedicated refrigerator, not in a refrigerator that also contains flammable liquids.
For pyrophorics stored in protective solvent, kerosene, or oil, check on a regular basis to ensure that there is sufficient liquid.
Do not return pyrophoric chemicals to the original storage container as small quantities of impurities can cause fire or explosion.
Store all liquid pyrophoric chemicals in secondary containers.

Disposal

Unused pyrophoric chemicals and laboratory equipment contaminated with pyrophoric chemicals must be hydrolyzed to non-pyrophoric products as part of each experiment. The end products must then be collected as chemical waste in a properly labeled waste container for disposal through EH&S.
Emptied containers of liquid pyrophoric chemicals must be triple rinsed with an inert dry solvent under an inert atmosphere. The resulting solvent rinsate must also be hydrolyzed to destroy any residual pyrophoric chemical and then collected for disposal as chemical waste. Allow the empty container to thoroughly air dry (several days) and then triple rinse it again. This rinsate must also be collected for disposal as chemical waste.

References and Additional Information

Sigma Aldrich Technical Bulletins:
1. AL-134, Handling Air-Sensitive Reagents
2. AL-164, Handling Pyrophoric Reagents
University of California, Irvine, EH&S Department, Standard Operating Procedures (SOPs) Resources.
Written SOP: Using Pyrophoric Reagents.
University of California, Los Angeles Video: Pyrophoric Liquids
Pacific Northwest National Laboratory, Handling Pyrophoric Reagents
University of California, San Diego Videos:
1. How to Handle Pyrophoric Reagents, Part One: Getting Ready
2. How to Handle Pyrophoric Reagents, Part Two: Transferring Pyrophoric Liquids
University of Iowa: Pyrophoric Reagents Handling in Research Labs

Chapter 6: Identifying Peroxide-Forming Chemicals