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Proceedings of the 4th National Symposium on Biosafety

Safe Practices and Procedures when Working with Chemical Hazards

Charles Miller, DVM, PhD
Medical Toxicology
California EPA
4221 Strickland Mine Street
Placerville, CA 95667
916-324-3474

We are going to discuss, "Chemical and Physical Hazards in Animal Research", emphasizing safe practices and procedures. What we're talking about is risk and safety. If you want it perfectly safe, if you do not want any risk, you don't attempt to perform the work. But, that is not practical. We can minimize risk and safely perform the research. The minimization of these risks is what we will spend the remainder of this session discussing.

There are many correlations between biosafety and chemical hazard assessment. One divergence is the OSHA Hazard Communication Standard and other regulations that require or mandate certain activities when working with chemicals. These are activities that may not have to be performed relative biosafety concerns.

These activities include hazard identification, material safety data sheets, labels, a written hazard communication program, employee information and training. Chemical toxicity experiments require these activities. So, there are drivers. The choices are limited. Hazard determination is very applicable to both chemical and physical hazards. How can one regulate, design an experimental protocol or plan employee training if you haven't identified the hazards.Specifically, we will focus on the physical and chemical hazards associated with animal facilities. We'll start with the physical hazards.

There are physical hazards associated with working with animals. These hazards include those associated with the work environment and some work practices. I wanted to first talk about working with animals. Trauma, bites, scratches, and injuries from falls or equipment are all associated with work with animals.

This slide of a gorilla reminds me of the jaw strength. These animals are incredibly quick and strong. They can inflict major trauma. This primate's digit's nail represents a pretty good scratch. All of the animals, with the exception of hoof-bearing animals, rabbits, rats, mice etc., have this capability of inflicting a nasty scratch or bite. It wouldn't keep surfacing if it wasn't a reality. This slide reminds us of the difference in mass between large animals and humans. We can be crushed.

Working around large animals represents the potential for some type of trama. In considering caging, there are sharp edges, pinch points, and the animal that can scratch, cut and pinch.

In considering the chemical hazards associated with animal research, several types of hazards need to be considered. Hazards are associated with cleaning agents, disinfectants, pest control agents and experimental agents. Pest control programs must be in place but represent a potential contamination hazard.

Most chemical concerns are associated with our research. We typically don't have the exact type of containment in our facilities that we need. Sometimes we make due with facilities that do not have the appropriate numbers of air changes, etc. Those are one set of problems covered in another session. Let's spend a moment talking about chemical toxicity. It's already been mentioned, but there are thousands of chemicals. Chemicals really don't allow themselves to be lumped all that well. Chemical toxicity is very chemical specific. The chemical or compound that we're working with dictates the appropriate procedures and ractices that we use to maximize safety, often dictating whether we increase or decrease personal protection equipment, etc. So it's chemical specific.

Paracelsus, the father of toxicology stated, "All substances are poisons, there is none which is not a poison; the right dose differentiates a poison from a remedy". I would add that route also plays a major role with this observation. Toxicity is dose and compound specific. If there are no exposures, there are no problems. There are cases in the literature where people have consumed enough water that they died.So is water toxic? Yes, if it's the right dose. We need to keep that in mind when considering exposure in the animal facility.

Routes of exposure

Dermal – Skin punctures may occur by animal bites. We also use sharps that may be contaminated with chemicals. There are some situations where we utilize intravenous delivery systems for giving a chemical via a needle and syringe or for collecting a blood sample. Depending on when your taking the sample you may still have principle toxic material present in the venous system. We may have toxic metabolites present. Sometimes we forget this. We are using a syringe and needle to acquire samples. We can possibly have the problem of sharps and sticks. This is an old concept relative to zoonotics but it should be considered in the chemical situation.

Inhalation – We've already considered bedding. The main point is that toxic metabolites and/or principle toxic materials may be found in the litter. When animals fluff their litter they can create aerosols. They contaminate litter in a number of ways, mostly by urine and feces. Depending on what species we're dealing with, urine volume and the presence of potentially toxic chemicals represent potential containment and exposure problems.

This discussion is relevant to chemicals and some of the potential hazards we need to consider. Do we know biologically what metabolites to expect? What is indicated in the literature? What will the liver do? What kind of detoxification is anticipated? We can create potential inhalation problems from these aerosols that include toxic chemicals. We then must consider personal protective equipment. I also wanted to mention saliva. When you use an anesthetic in animals for restraint or surgery you may see saliva pooling outside the mouth. This salia may also have toxic metabolites present, posing some potential dermal risk.

Clearly, when considering excretions, the most important are urine and feces. Unmetabolized chemicals, metabolites and radiolabled chemicals do pass through in the urine and feces and must be considered in a hazard assessment.

Ingestion – Ingestion doesn't happen much anymore, now that we have mouth pipeting and eating, smoking and drinking in research areas under control. However, we need to keep all personal protective equipment in place. One of the messiest things I've ever seen is the necropsy room. Most of the mess is not planned. Things just splash around. Animals, especially large animals, don't lend themselves to being moved, pushed and shoved around. Large rumens full of fluid can result in splashes possibly resulting in oral ingestion.

Absorption – As a route of exposure, absorption plays a big role with chemicals. This is particularly important as we deliver a chemical during animal exposure. Also, if we're mixing a chemical into feed. Dust is an issue. The appropriate personal protective equipment must be used to keep skin exposure and potential absorptions to a minimum. There are not that many zoonotic organisms that get past the skin. With chemicals this is a big potential. We can get rather sizable exposures depending on the chemical. This is another important consideration to keep in mind as we think of chemicals and their use in the animal research.

Reproductive toxins – How many chemicals are reproductive toxins? The number is increasing. Previously we considered a standard few that included anesthetic gases. There are numerous others that are emerging that effect both males and females. We used to consider, protect and take care of the pregnant employee and fetus. But there is an increasing list of chemicals and their metabolites that we recognize as reproductively toxic for both men and women. Many other we don't have data on. I think arguably we need to keep our guard up, use universal precautions, and use good scientific thought in these situations. It's imperative that we train people, especially animal handlers, so they know what they are dealing with.

Animal Restraint

Animal restraint should be a part of personnel training in animal research. We've found in the facilities that I've worked in that it is important to have "hands on" training for the restraint of different animals. We find that it helps to team up a new employee with a more experienced animal handler. Each animal species is going to have their own type of restraint techniques. We don't always want an animal chemically sedated. So we utilize mechanical or physical restraint. We might utilize restraint cages depending on the situation. Exposure for delivering a chemical or drawing a sample from an ear may require another means of physical restraint. The use of personal protective equipment when restraining an animal will be very individual and situation specific.

A whole session will be devoted to sharps. Generally, we try to keep anything sharp or breakable out of the animal arena. Lastly, one should always attempt to minimize aerosols. This applies to minimizing aerosol exposure chemically and biologically, in all aspects of changing animal caging, their litter, spraying down walls, washing floors and those things associated with research animals.

In terminating an experiment, there are numerous similarities between biosafety and chemical safety. For some toxic materials or chemical hazards there are different considerations. We need to be humane in our experiments termination. We talked about necropsy. Let's discuss animal disposal. Ninety percent or more is still done by incineration. The chemically toxic material in the animal are incinerated.

Sanitation and decontamination are typically routine. Occasionally, we need to deal specifically with a particular chemical's considerations, ie. if secondary metabolites or perhaps the primary chemical itself is shed in the urine or feces. For the most part it's just a general routine decontamination. We take advantage of huge volumes of water for the disposal problem. Relative to incineration and the chemically contaminated waste water, "the solution to the pollution is still dilution."

In summary, working with animals poses risks. We've identified some of those risks throughout the sessions today. Some risks that are specific to chemicals, are not unlike what we would find in a zoonotic situation or when working with viable biological agents. We must continue to be vigilant about the recognition and reduction of all risks in animal research.

Symposium Contents


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