Identify and evaluate hazards

The first step in risk management is to identify hazards in and emanating from the workplace. If this has never been done, it may be a formidable task, especially if there are old reagents or chemicals in poorly labeled containers. Anything that is unidentifiable or questionable should be set aside for disposal. Identification of hazards goes beyond making a chemical inventory, although that is a significant part of the effort. Electrical, mechanical and biological hazards are also included. In this initial identification stage, include the nature of the hazard(s) with the name, its location and the procedure(s) involved with its use. If no current use is found, then dispose of the item.

For hazardous chemicals, data sheets are available in most countries, and available from databases on the Internet. A file of data sheets should be kept in a secure location, and employees must be given reasonable access to it. It is also advisable to keep a duplicate file readily accessible in the laboratory in case of emergencies. Some reagents found in storage areas may be obsolete; sheets will be impossible to find for these. This creates a problem with no simple solution, because legitimate disposal may require having a data sheet, yet keeping the chemical also dictates that a sheet be on file. You will have to create one, or hire a qualified firm to do that for you.

Evaluate the severity of each of the hazards. What is the volume or magnitude of the hazardous item? How much is used per day (or some other meaningful unit of time)? Now put that information together with the data sheet. These are written for industrial-scale exposures, and you must weigh that against the scale of use in your laboratory. This evaluation must include risks associated with spillage and disposal as well as normal use. The hazards of a bulk container of formalin emptying onto the floor of a laboratory are quite different from spilling a 30 ml specimen container in a dermatologist’s office. Likewise, emptying hundreds of small formalin-filled specimen containers into a disposal drum or sink might present far greater exposure risk than handling each one during grossing. Do not underestimate risk, but keep the assessment proportional to scale and scope of operations.

Plan to minimize risk

Once the hazards have been listed and evaluated, decide how to reduce risk. Each item should be scrutinized, not just those offering the greatest dangers. Prioritize later. The goal is to reduce risks to acceptable levels, preferably through a cascading series of options that become progressively more burdensome and expensive. Work practice controls are the best way to tackle the problem; when pursued aggressively and with commitment at all levels of the institution, they usually are the only changes needed. Work practice controls involve eliminating, reducing and recycling everything possible. If they do not succeed, engineering controls should be implemented. These involve ventilation systems, fire protection devices and other expensive alterations to the facility. If all of these measures fail or are impossible to accomplish, personal protective equipment (PPE) must be used as a last resort. PPE should never be the first choice, although it may seem the most obvious way to protect workers.

There are several ways to reduce risk, the first of which should be to eliminate the hazard altogether. The list of obsolete chemicals in some of our labs is growing rapidly; how many does your laboratory still use? Remember using benzene and dioxane? No? Then do not be surprised in another few years to have histologists and biomedical scientists who never used xylene, toluene, chloroform, methacrylate, picric acid, uranyl nitrate and formaldehyde. A surprising number of laboratories are free of one or more of these highly dangerous substances and a few have eliminated all of them

Practically every hazardous chemical can be replaced today with a safer and technically superior substitute. The question is not whether it can be done, but if it might be done. The obstacle is rarely technical feasibility; most likely, it is human obstinacy. The notion that substitutes are not as good has been debased so often in everyday life that it is a wonder that it persists so strongly in the medical profession. Antifreeze, correction fluid, nail polish, hard surface cleaners, cosmetics, contact lens solutions and gasoline are just a few of the thousands of common materials in our lives that have undergone radical reformulation. In all cases, the products are safer, many work better, and some are less expensive.

If elimination of a hazard is out of the question, consider reduction. This will involve procedural changes, so be sure to weigh all implications before pushing ahead. A common idea for reduction is to use smaller specimen containers for fixation. Recycling is a final option for risk minimization. The volume in use at any given time might not be reduced, but the amount involved in storage and disposal will be cut drastically.

The plan must include justification to managers. Rationale for change should not rely solely upon improving safety. Financial considerations weigh heavily in any business, and could be your strongest argument for change. While many changes will cost more money initially, the long-term benefits are usually easy to calculate. For example, formalin substitutes are more expensive than formalin, but their use creates significant savings later. Workplaces and personnel do not need to be monitored for hazardous vapors, and disposal costs are usually reduced to zero. Less tangible but nonetheless real are the cost benefits of a healthier work force.

Implement the plan

Having a plan will do no good unless it is implemented. Prioritize the changes described in the plan. While easy changes should be tackled immediately, do not put off the challenging items that carry high health or environmental risk. Achieving financial gain quickly will help your cause, so be sure to include something at the outset with immediate positive economic impact.

Design standard operating procedures for working with hazards

Nearly all laboratories operate under a set of written, standard operating procedures (SOPs) mandated by a variety of accrediting or regulatory agencies. Detailed procedures for handling hazardous substances certainly should be central in these procedures, but other topics ought to be addressed as well. Personal hygiene practices should be a subconscious part of every workers’ behavior, but must be spelled out in the SOPs. Define the criteria for invoking the use of specific control measures, such as the use of protective equipment. Describe how to assure that fume hoods and other pieces of protective equipment are functioning properly. Make provisions for employee training, medical consultations and medical examinations. Detail spill procedures; define the kinds of spills that should be handled by laboratory workers and those too serious for anyone except trained HazMat responders. Establish a qualified officer or committee of qualified people to develop and administer these safety procedures.

Train personnel

Safety training is mandated by a variety of governmental regulations in several countries, and should be part of every department’s personnel practices. Trained people work more safely, efficiently and economically. In addition, the threat of employee litigation against the department is reduced. Regulations rarely address the issue of who should provide the training. In the past, it was common for one of the technical staff (usually the supervisor) to do this, that person obtaining the information as best he/she could. It is preferable, however, to have the trainer who is specially educated and experienced in health and safety matters.

Training must include general practices and may deal with very specific topics such as respirator use, handling select carcinogens, and working with formaldehyde. Each employee should sign a form verifying that training was received, a copy of which becomes part of the employee’s permanent record. The employee’s name, date and subject of training should be included on the certification form. Yearly retraining should be mandatory and documented. New employees, or employee’s assigned new hazardous tasks, must be adequately trained before beginning work.

Periodic reviews

On at least a yearly basis, all SOPs, risk assessments and training programs should be reviewed and updated as needed. Each written document should bear the date of creation and latest revision. Continue to minimize risks. Address any new risks that occur when different hazardous materials are brought into the workplace. Revise risk assessments and protocols to accommodate increased use of hazardous substances, especially as workloads increase.

Record keeping

Regulations often prescribe what records must be kept and for how long. It is prudent to record everything that pertains to regulatory compliance, risk assessment, causes and prevention of occupational illness or injury, employee health and safety training, exposure monitoring, occupational medical records, personal protective equipment and hazardous waste disposal practices. Records should be kept indefinitely, although 30 years past the duration of a worker’s employment is the term often prescribed by regulatory agencies. If in doubt, consider this: for how long would you want your estate to have access to health and safety records relating to your employment?

Occupational exposure limits

Most chemicals are hazardous to some degree; the question really is how hazardous are they? In other words, what would a safe level of exposure be? From many years of actual industrial experience, various agencies have developed standards for exposure to widely used chemicals. Generically, these are called occupational exposure limits, but each agency refers to its own values by unique names. OSHA’s Permissible Exposure Limits (PELs) are based upon scientifically based recommendations from the National Institute of Occupational Safety and Health, or NIOSH (2003), but are also influenced by special interest groups and Congressional actions. OSHA limits therefore typically are more lenient. Another source of exposure limits, called Threshold Limit Values (TLVs^®) is ACGIH^®, the American Conference of Governmental Industrial Hygienists (2004). These limits are more widely used around the world for occupational standards.

An exposure limit is the maximum allowable airborne concentration of a chemical (vapor, fume or dust) to which a worker may be exposed. Presumably, it represents the concentration at or below which it is safe for most people to work; there will be individuals who react adversely below the limits because of hypersensitivity.

It is important to realize that exposure limits are properties of the worker and the workplace combined. They are not simply the maximum limits of vapor, fume or dust in the workplace; they are the maximum limits of exposure. This is especially important to consider when monitoring exposure levels. Monitor employees, not the workplace. Monitoring devices should be positioned as close as possible to the worker’s face in order to capture actual breathable quantities of hazardous material. For example, airborne levels of formaldehyde vapor a few inches above a grossing station’s cutting board may be much higher than concentrations at nose level, especially with well-designed ventilation.

Biological exposure indices

Can a worker determine if significant exposure has occurred? Can the chemical in question be detected in the worker by a clinical test? In a few instances, the answer is ‘yes’. ACGIH^® has established Biological Exposure Indices (BEIs^®) as maximum values of analytes determined from clinical tests on exhaled air, urine or blood for a variety of hazardous chemicals, but only four are pertinent to histology: N, N-dimethylformamide, methanol, phenol and xylenes. Consult the latest booklet issued yearly by ACGIH^® for details on the first three chemicals.

Because xylene is used so pervasively in histology, and so many histologists are concerned with its effects, further information is presented here on this chemical. The isomers of xylene are metabolized to methylhippuric acids, which can be measured in exposed workers’ urine. The BEI^® for xylenes is 1.5 g methylhippuric acids per g creatinine. Samples are collected immediately at the end of a work shift.

BEIs^® are not intended to be used in diagnosing occupational illness. They are not maximum safe permissible values. Rather, they are to be used as indicators that workers may be exposed to significant concentrations of harmful substances, particularly if a worker or a group of co-workers repeatedly show values of the analyte at or above the BEI^®. For xylene in a well-ventilated histology lab, high methylhippuric acids in urine would probably indicate significant skin exposure.

Types of hazard

Systems of classifying the hazardous nature of chemicals range from simple pictographs with numerical ratings to comprehensive lists of formally defined terms. Even within a single country, government agencies may differ in how hazards are defined. While no single system will suffice worldwide, the following terms do have nearly universal meaning and should serve on a practical basis for describing the hazards encountered in histology. For convenience, hazards are first divided into two broad categories, health and physical. The latter certainly have ramifications for health, but present more immediate problems for storage, handling and building codes.

Toxic materials are capable of causing death by ingestion, skin contact or inhalation at certain specified concentrations. These concentrations vary slightly according to the agency making the designation, but differences are insignificant to the histologist. Some countries use the term poison when referring to this category. Toxic chemicals pose an immediate risk greater than the previously covered hazards, and some are so dangerous that they are given the designation highly toxic. Methanol is toxic; chromic acid, osmium tetroxide and uranyl nitrate are highly toxic. Use extreme caution when handling toxic substances; avoid highly toxic ones if possible.

Chemicals causing specific harm to select anatomical or physiological systems are said to have target organ effects. These are particularly dangerous substances because their effects are not immediately evident but are cumulative and frequently irreversible. There are numerous histological relevant examples: xylene and toluene are neurotoxins and benzene affects the blood. Reproductive toxins are especially prevalent (chloroform, methanol, methyl methacrylate, mercuric chloride, xylene and toluene, to name a few) and may warrant special consideration under occupational safety regulations of some countries.

The remaining hazard classes pertain to physical risks. Combustibles have flash points at or above a specified temperature. Flash point is the temperature at which vapors will ignite in the presence of an ignition source under carefully defined conditions using specified test equipment. It is a guide to the likelihood vapors might ignite under real workplace conditions. Flash point is not the temperature at which a substance will ignite spontaneously. Different countries and various agencies within those countries have their own unique values for the specified temperature. In the USA, OSHA defines it as 38°C, while the Department of Transportation uses 60.5 °C. Combustible liquids pose little risk of fire under routine laboratory conditions, but they will burn readily during a fire. It is better to choose a combustible product over a flammable one if all other considerations are equal. Clearing agents offer this choice.

Personal hygiene practices

There must be no eating, drinking or smoking in the lab. Application of cosmetics other than hand lotion likewise has no place within the laboratory setting. Wash hands frequently, but keep skin supple and hydrated with a good lotion. If hazardous powders have been handled, wash around your nose and mouth so that adherent particles are not ingested or inhaled. Solutions must never be pipetted by mouth.

Labeling

Every chemical should be labeled with certain basic information; proper labeling of all containers of chemicals is mandated in some countries. Most reagents purchased recently will have most of the following already on the label, but older inventories may lack certain critical hazard warnings. Remember that solutions created in your laboratory must be fully labeled. Minimum information includes:

When putting a reagent’s name (or names of ingredients) on the label, use terminology that will be useful to those needing the information. In histology, we have many reagent names that are unfamiliar to chemically knowledgeable people who might be involved in an emergency. This is why it is so important to list ingredients, using names with widespread acceptance in the general field of chemistry; for example, use formaldehyde for formalin, acid fuchsin and picric acid for Van Gieson’s, and mercuric chloride, sodium acetate and formaldehyde for B-5.

Commercial products in their original containers will have the name and address of the manufacturer or supplier. If you put the material into another container, even ‘temporarily’, include this information on the new label. Chemicals in ‘temporary’ storage conditions have a bad habit of remaining there for years after laboratory personnel have moved on.

If the reagent is made in the laboratory, indicate who made it and when. Traceability could be critical if other information is lacking, as in the case of a Coplin jar of ‘silver stain’ left in a refrigerator. Is the solution one of those that is potentially explosive? Does anyone know which silver solution it is?

Many laboratories use small self-adhesive labels that say ‘Received: ——’. These are dated and affixed to each incoming container. Similarly, an expiration date should also be included for those chemicals that do not have an indefinite shelf life. Most inorganic compounds and many non-perishable organic chemicals are good for many years, but mixtures frequently deteriorate in a shorter time. Information on shelf life is hard to come by, and the best source is your own experience since each laboratory has different conditions and perhaps slightly varied formulations. Kiernan (1999) has included shelf-life data from his own extensive experience, which should serve as a good first approximation for your use.

Hazard warnings at a minimum should include the designations listed in the preceding section. This is the simplest and least ambiguous system. Pictographs (flames, corroding objects, etc.) are not universally recognized; some are obscure as to their meaning. Hazard diamonds are popular but carry risks of misinterpretation, especially since there are several systems in use. When there is an emergency, people may not think clearly or have time to figure something out. They need immediate access to the nature of the danger, and nothing provides that so effectively as the printed word. Briefly worded safety precautions may be appended to the hazard warning: for example, irritant, avoid contact with skin and eyes.

A multicultural workforce, not all of who may have the same native language, staff many labs. It is prudent to accommodate their needs by providing multilingual hazard warnings. Again, in an emergency you want no impediments to prompt and correct action.

Warning signs

Various countries have established different guidelines or mandatory regulations involving signage, so specific recommendations cannot be given here.

Protective equipment

There are certain general guidelines for clothing suitable for laboratory work that should be considered before protective equipment. Secure, close-toed footwear should be mandated; open-toed shoes and sandals offer no protection against spills or dropped items. While nearly all fabric today is resistant to destruction by histological solvents, such was not always the case. Certain early acrylic and acetate fibers dissolved almost instantly when in contact with xylene or toluene, creating a great deal of embarrassment when tiny drops of solvent hit the cloth. The possibility that such fabric still exists is real enough to take heed.

Aprons, goggles, gloves and respirators are the personal protective equipment (PPE) most likely to be used in the histology laboratory. In some countries, law for certain hazardous situations requires specified PPE. The following set of recommendations should be a routine part of general laboratory hygiene and will satisfy the most stringent regulations. When specific requirements exist for certain chemicals, such information will be included below in the section detailing common histological reagents. Aprons should be made of material impervious to the chemicals being used. Simple disposable plastic aprons are usually quite satisfactory, although heavy rubber aprons may be warranted when handling concentrated acids. Cloth laboratory coats are suitable only for protection against powders or very small quantities of hazardous liquids. Do not use them for protection against formaldehyde.

Goggles should be chosen specifically for each worker to accommodate the diversity of facial shapes and prescription glasses. Goggles not only come in a variety of sizes and shapes but also they are made for different functions. Choose only vented splashproof goggles for routine work in histology. These allow for ventilation, which reduces bothersome fogging of the lenses, but the vent holes are baffled so that splashing liquids are not likely to reach the eyes. Never cut holes in goggles to improve ventilation, as this defeats the protective function of the equipment. For severe conditions of exposure, wear a faceshield over splashproof goggles; never use a faceshield without the goggles. Finally, safety glasses are no substitute for goggles when handling hazardous liquids.

The issue of contact lenses arises frequently in discussions about eye protection (American College of Occupational and Environmental Medicine 2003). If liquids with no irritating fumes are being handled, contact lenses may be used safely in conjunction with appropriate goggles. Conventional goggles offer no protection against harmful vapors, which can become trapped beneath the lenses, causing corneal damage. If your eyes sting or water, your inhalation exposure is almost certainly beyond permissible or prudent limits. Regardless of whether you wear contact lenses, do not work under those conditions, even for brief periods.

Gloves are the most controversial PPE, and misinformation abounds. It is important to understand how gloves work, so that informed decisions can be made about glove selection. Glove material is rarely completely impermeable; it delays penetration of harmful material for a time sufficient to provide adequate protection. Chemical resistance refers to how well material holds up in the presence of solvents, but says nothing about how readily substances move through the material. In most cases, liquids rarely penetrate intact glove material. The vapors are the problem, both because they penetrate more efficiently through gloves and skin, and because the worker usually cannot detect them. Reputable manufacturers of gloves evaluate their products in standardized tests, measuring the time it takes for detectable amounts of a particular chemical to appear on the far side of the material. This is called the breakthrough time, and it increases non-linearly with glove thickness. A glove twice as thick as another made from the same material will not have a breakthrough time that is double that of the thinner glove. Schwope et al. (1987) present the most comprehensive listing of data on this subject.

Latex is one of the most permeable of all glove materials. Thick (8 mil) rubber gloves have a breakthrough time of 12 minutes with formaldehyde solutions. Latex surgical gloves are so thin (1.0–1.5 mil) that they offer no effective protection against formaldehyde or histological solvents. These gloves are suitable only for protection from biohazards. Keep in mind the startling increase in the incidence of latex sensitization, which has accompanied the widespread use of these gloves since the beginning of the AIDS epidemic.

Nitrile gloves are the best option for histological use. They are available in surgical-type thinness for brief intermittent exposures where fine dexterity is necessary. Exposures that are more serious can be safely tolerated with 8 mil nitrile gloves. Remember, however, that no glove material is effective against all classes of chemicals, and nitrile is no exception. Some chemicals in wide histological usage (xylene, toluene, chloroform) will permeate nitrile in seconds.

Respiratory protection against chemical vapors should rarely if ever be needed except in emergencies. Regulatory agencies stress that respirators are the protective equipment of last resort. No one in histology should be in a workplace whose vapor levels are even transiently higher than the PELs. Wearing respirators is uncomfortable, expensive and fraught with compliance hassles. Leave them to the people specially trained not only in respiratory use but also in dealing with such dangerous environments.

In the following discussion, the word ‘should’ is used, but substitute ‘must’ in countries having stringent respiratory protection standards. Workers should receive special training for wearing respirators because of the complexities of proper usage. Each worker needing this level of protection should be individually fitted with a respirator that exactly fits the contours of the face. The efficacy of the fit is then assured through a series of complicated tests that should be documented and repeated on a periodic basis. Workers should undergo medical evaluations and respiratory function tests to determine if they are physically qualified to wear respirators. Cartridges for respirators must be chosen carefully for the chemical environment. Both the type of chemical and the vapor concentration are vitally important considerations. Respiratory protection from airborne infectious materials is another matter altogether. Surgical masks are unacceptable because they fit poorly and have too large a pore size to filter out aerosols. HEPA (high efficiency particulate air) filters are suitable. Workers wearing HEPA masks may have to comply with applicable provisions of respiratory protection standards.

Ventilation

Ventilation is the foremost engineering control; ensuring proper airflow through a laboratory is the first critical step in improving working conditions. Every laboratory scientist should be aware of the following basic principles. For further details on hood design and placement, see Dapson and Dapson (2005) and Saunders (1993). Laboratories should have two separate systems of ventilation, one for general air circulation (often combined with heating and air conditioning and called HVAC), and the other for local removal of hazardous fumes. They must work in concert to be effective, and must not merely shift the noxious vapors to another part of the facility.

General ventilation is for the physical comfort of the occupants of the room. Each hour, the entire volume of room air should be exchanged 4–12 times. That air should not contain significant quantities of hazardous vapors. If such vapors are originating somewhere in the room (from a grossing area, for instance), they should be dealt with at their source with an independent system of local ventilation.

Properly designed chemical fume hoods enclose the emission area, isolating it structurally and functionally from the rest of the room. A motor somewhere in the ductwork (preferably far from the hood) moves air directly to the outside. A sliding door (sash) usually fronts the system, and is an integral part of the way it works by controlling the face velocity of air entering the enclosure. It is a common misconception that high face velocities are good. In fact, strong airflow may create such turbulence inside the hood that contaminated air spills back out into the room. For vapor levels usually encountered in histology labs, a face velocity of 80–120 linear feet per minute is ideal. Control this by adjusting the height of the sash. As lifting the sash enlarges the opening, face velocity declines. Either a vaneometer built into the hood or obtained as an inexpensive handheld device measures face velocity. Always keep the sash at least partially open (unless the hood is designed to admit room air from another port) to prevent overtaxing the motor.

Improperly designed hoods will not be able to achieve optimal face velocity with the sash opened to a comfortable working height. Avoid these literally at all costs, for your facility’s money will only be wasted, giving you a false sense of security. There are important dimensional considerations that determine a hood’s effectiveness: the hood will develop dangerous eddies if too shallow and may not be able to move the full volume of air if too expansive.

There are other, external factors that influence how a hood works, and all center on the air supplied to the face of the hood. It should be obvious that a device removing air from a workplace must have a supply to draw upon. This is in addition to the amount required by the general ventilating system to exchange 4–12 room air changes per hour. Heating and air conditioning must also be balanced to account for the removal of air through the hood. Location of a hood is critical. Airflow into the face should be smooth and unimpeded. Surprisingly strong crosscurrents are generated by doors opening and closing, or by people walking by. Even the draft from general HVAC ducts can adversely affect hood performance. Any of these disturbances can draw harmful vapors out of the enclosure into the room, even against a net inward flow of air. Locate the hood, and by inference the hazardous work area, out of main traffic patterns and away from HVAC ducts.

Do not use fume hoods as storage or disposal devices. Objects within a hood disrupt airflow, and may block important air passages. Containers that emit vapors should not be placed within a hood except as a temporary safety measure. Remove the offending substance as soon as possible and put it into a secure container. Finally, do not put a waste chemical into a hood for evaporating it away unless there is no alternative in an emergency. Doing so is probably a violation of environmental regulations, and it may exceed the capacity of the hood to carry fumes away safely.

Ventilation devices other than fume hoods are used in histology labs; few are suitable unless vapor levels are already low. A non-enclosed system, such as a duct located above or behind the work area, may be powerful enough to draw contaminated air away from the worker as long as no crosscurrents are generated, but that is an unrealistic assumption. Workers must move about, and that usually destroys the effectiveness of unenclosed devices. Hoods that return air to the room after passing it through a filter may be suitable for localized workstations generating modest vapor emissions. Filters must be chosen with care. Vapor levels will dictate the size needed. Formaldehyde is not effectively captured by the filtration media used for solvent vapors. Filters become loaded and must be replaced, but how often this occurs is usually a mystery until odors are noticed out in the room. Since most workers in histology labs have impaired senses of smell, dangerous vapor levels may accumulate before anyone detects them. If filtration devices must be used, figure out how to determine effective life of the filters and establish a strict replacement regimen.

Air purification systems based upon ozone should not be used. They generate a chemical that is more hazardous than most of the fumes found in histology labs: ozone has a Ceiling Limit of 0.1 ppm according to ACGIH^®. Further, ozone from these purifiers does not seem to be effective in destroying formaldehyde vapors (Esswein & Boeniger 1994).