Occupational Health HazardsAs in classical industry, the conditions of the pathology workers should be optimized, as

well as the quality control. It is imperative to consider and try to optimize the conditions of theenvironment in which quality work is expected. This optimization necessitates the knowledge of thehazards and expectations.

The major occupational health problems encountered in pathology departments arebiological, chemical, physical, and ergonomic hazards.

In Pathology departments, most encountered chemical substances are formaldehyde(FA),xylene (Xy) and latex. There are also aromatic amins at smaller rates and substances likemetacrilate and glutaraldehyde in some departments.

Formaldehyde

Formaldehyde (HCHO) is a colourless and flammable gas. It is obtained by the oxidation ofmethyl alcohol (1,2). It is also known as methanal, methylene oxide, oxymethylene,methylaldehyde and oxomethane (1). It dissolves in water easily. Its 37% solution is calledformaline (3,4). Formaldehyde can be polimerized to substances like paraformaldehyde andtrioxane when combined with water. To prevent this, about 15% methanol is added. This shouldalso be considered in toxic effects (1,5). Formaline vapour concentration in air is measured withppm (part per million) and 1 ppm is equal to 1.248 mg/m3 (presence of 1,248 mg formaline in 1cubic meter air is called 1 ppm) (3). Formaline is metabolized to formic acid in a very short time as1,5 minute (3). Formic acid is excreted through kidneys or changed into carbon dioxide and water.

Formaldehyde is present in many nutrients (such as fruits, coffee) (6). When given to ratsat carcinogenic levels, there was no increase in endogene levels (3). In addition to its presence innutrients, it is used in industries such as chemistry, paint, plastics, construction materials, textile,paper and cosmetics, and it is found in exhaust smoke, cigarette (about 0,38 mg in a pack) andfire smoke (3-6). Formaldehyde production in England is estimated as 60-145 thousand tonnes peryear (4).

When formaline vapour measurements are taken, it should be specified whether themeasurement is done at work level or breathing level. Its highest concentration is in autopsy andspecimen dissection rooms. Weekly exposure dosage of technicians has been found 0.6-1.3 ppm inmeasurement of dosage against time. This may increase to 8 ppm according to the conditions(2,3).

As specified in the USA (by Occupational Safety and Health Administration-OSHA), themaximum level (Threshold limit value-TLV) for 8-hour working period (Time weightedaverage-TWA) is 0,3 ppm (2). This value is for breathing zone. TLV-TWA value for measurementdone at maximum is 0,5 ppm (3,4) (Picture 1).

Picture 1: TWA and STEL sample graph. In the measurement shown with dotted line, it means it isover OSHA threshhold level because STEL value is exceeded. In the measurement shown withbroken line, TWA value is exceeded and as the 8-hour mean of this (area below the curve) is aboveTWA margin value, it means that mean is exceeded. In the measurement shown with straight line,although TWA value is exceeded from time to time, it is accepted as in normal limits because STELvalue is not exceeded and 8-hour median value (area belw the curve) does not exceed TWA.

Peak limit for the condition that it should not be more than 30 minutes a day (TLV-ShortTerm Exposure Limit-STEL) is 10 ppm (3). Latest values accepted by OSHA are 0,75 ppm forTLV-TWA, 2 ppm for TLV-STEL. It has been claimed that in the embalming and autopsy rooms, andeven in histology rooms these limits are exceed (3). Irritant effect starts when the concentration isabove 1 ppm (1,2). This effect is reversable when there is no contact. Effects of FA aredosage-dependent (Table 1).

Table 1: Side-effects of formaline related to dosage (3,5).

FA concentration (ppm) Side effect0.05-1.0 Bad smell0.05-2.0 Eye irritation, neuropsychic effect0.1-25 Nose, throat irritation5-20 Watering of eye, dyspnea, cough, inflammation in nose, eye andpharynx+20 Pulmonary edema, pnumonia+100 Death

It is not known by which mechanism it shows its toxic effect. However, it attaches aminogroup in amino acids and forms hydroksimethyl aminoacid and proton (H+ or acid), and showsmicrobe killing effect by this way (1). In high concentrations, as we know, it precipitates proteins.DNA-protein cross bounding occurs also after exposure through inhalation (1). These effects arethought to cause irritation.

We can summarize the toxic effects of FA as membrane irritation, contact dermatitis andmutagen-carcinogen effects. In a cleaner who mobbed the morgue room with 37% formaldehydeand 10% methanol, paralysis, pulmonary edema, cerebral anoxia and permanent mental deficiencyhave been developed (5). Eye irritation starts at 0,24 ppm, and it becomes impossible to stay inthe environment at 6 ppm. However, these margin values for both smell and eye irritation mayincrease to higher levels by the time with the adaptation of the person (3, 4). Margin is higher inpeople who smoke, which means they feel less irritated. It may cause permanent damage whenspringed to the eye, and should be washed immediately (4). Dermatitis is a frequent side effect.Asthma related to FA is rare but is a real case (3,4). Neuropsychic effects are on memory, sleepand behaviour pattern (3).

In a study, decrease in pulmonary functions and behavioural disorder were diagnosed inhistology technicians but these did not find acceptance later on. Decrease in pulmonary functionsdoes not affect physical capacity and this effect is for a short time. In chronic exposure, it effectsrespiratory functions and shows irritative effect. In a study, it was observed that exposure lessthan 10 years does not affect basal pulmonary functions (1). It was determined that it does notcause bronchospasm in asthma cases but appearance of symptoms related to FA is earlier (1).Sensitivity to irritant effect in smokers is less (1).

Allergenic reactions to chemical substances in atopic persons is more frequent but this isnot true for FA (2).

In a specialization thesis done by Pulmonary Diseases Department, 99 people working in 4hospitals in Izmir (13 anatomy, 86 pathology workers; 40 technicians, 11 specialists, 15academics) were evaluated in terms of FA and Xy exposures. Among these, 14% have beenworking in the field less than 1 year, 52% 1-9 years, 22% 10-19 years, 12% more than 20 years.41% of the cases were smokers. In 58% of the cases, respiratory system troubles, in 96%conjunctiva, in 74% nasal, in 25% dermal, in 87% neurological system troubles, and in 80%atopy, in 4% latex alergy were found. In the pulmonary function test scores, significant differencebetween the beginning and end of the week was observed. Formaldehyde patch test was also22,2% positive (2-4% in general population) (7). However, FA and Xy levels were not measured inthis study. Another important problem in this study and other similar studies (8) is that smokingfactor can not be eliminated.

There are number of studies related to other effects of FA, and we come acrosscontradictory results in some of these studies. There are related resources for more informationabout this (1). To give a short summary, FA inhalation may cause intestinal cramp, flatus, bloodyfeces. In experimental animal models, it was found that it causes weight loss in chronic exposure.Again, in chronic exposure, increase in autoantibody levels was observed. In high concentrations, itcauses decrease in motor activities (1). General findings of the studies are in the direction that FAdoes not have any effect on cardiovasculer system, musculoskeletal system, liver function tests,kidney and urine findings, endocrine and genital organs (1).

"Sister-chromatid exchange” was found in the lymphocytes of the medical students whohad been exposed to 1,2 ppm FA for 10 weeks (3, 9, 10). In vitro mutagenic effect was also shown(11). These two findings/diagnosis prove that it may have cancer causing effect. However, since itis metabolized very fast in human beings, this should be investigated (3). Its carcinogenic effect atvery high doses was shown in animals. When rats were exposed to 2 ppm FA for six hours everyday, 1% squamose cell carcinoma developed (3). In humans, as the dose that may causecarcinogenic effect cannot be tolerated, it is not possible to reach that dose. There was no increasein cancer incidence in 7680 workers who work at a place where FA was produced (3). In anotherstudy, there was a slight increase in nasal cancers (12). Relationship of FA with nasopharynxcancers seems reasonable, but its relationship with other cancers like lung cancer is doubtful (2).Possibility of a relationship of cancer with smoking and FA has been shown in industry, but this isnot proved by pathology. Nasal melanoma in 3 cases, one of which was a histology technician wasreported but this data was not (luckily) supported with epidemiologic studies (13). According to therecords started to be kept from 1943 in Denmark, no increase in nasal and lung cancers was seenin the workers of pathology, forensic medicine, and anatomy (2).

In the context of mortality there are contradictory results. In a study done inclusive of26561 people working in formaldehyde related works done by National Cancer Institute, nomortality increase was found in lung and prostate cancers, leukemia, brain tumor and all deathcauses. It was observed in this group that deaths from oral cavity and pharynx cancers were less(14). In similar studies, it was observed that there was no increase in cancer mortalities inanatomy and pathology workers. However, in another study, increase in death from brain tumorsin pathologists was observed, and also increase in chronic exposure and cancer mortality wassupported with other studies (1). Increase in hipopharynx cancer or lymphoid system cancermortalities was seen in some studies (14). On the other hand, in a survey done with 2079pathologists and 12944 technicians, increase in death from lymphoid and hematopoietic tumorswas found (2). No increase in cancer was observed in gravediggers and embalmers, but increase inmortality from rheumatic heart disease, skin, and colon cancer was found (3). However, there is noevidence that the cause of the increase is the FA. It is important to note that data is insufficient insome ways. Monitoring periods and population are not sufficient. Socio-economic level isdisregarded in comparisons.

Mutagenicity helps determining carcinogenic potential. Although the mutagenic effect of FAhas been shown (15), it is more acceptable that it is not carcinogenic for pathologists, anatomists,industrial workers, etc. (4, 6, 14). However, because of insufficient data and evidence from theanimal experiments that it is carcinogen, it is accepted that FA might be carcinogen for humans (by"The International Agency for Research on Cancer-IARC”, "The Environmental ProtectionAgency-EPA”, and "The National Toxicology Program”) (1).

Xylene

Xylene is also known as xylol and dimethylbenzene. It is used as a solvent in stain, rubberand leather industry. It is also used as thinner and cleaner for stain and varnish.It is found inaircraft fuel in small amounts. It is used in chemistry, plastic, synthetic fibre production, and papercoating (16). It evaporates easily and is flammable. Its smell starts to be felt at 0.08-3.7 ppm level(16). It can stay for months when mixed with soil or water. If evaporated, it can stay in air for daysbut it is broken into less harmful chemical substances with the sun light (16).

It passes into blood immediatelly after taken through breathing, oral or direct contact, isbroken in lungs and liver, and excreted via urine as methylhippuric acid. Exposure and level can bedetermined by checking the methylhippuric acid level in urine. Part of it is excreted via breathed air(16). It is excreted completely 18 hours after contact is ended. Excretion takes longer if it passedinto fatty and muscle tissue (16).

Occupational exposure upper limit determined by the USA (by "The Occupational Safetyand Health Administration”) is 100 ppm for 8 hours, and 15 minute exposure limit is (TLV-STEL)150 ppm (16).

Animal experiments conducted with Xy and research on humans have not provided anyevidence that it is carcinogen (16).

Its short-term high doses cause acute repiratory distress. Its lower doses may causeheadache, nausea, loss of appetite, fatigue and loss of coordination (16, 17). With long-termexposure it causes central system depression and contact dermatitis. In histology technicians,behavioral changes and findings regarding respiratory system were diagnosed (16, 18).Hematologic disorders found in some studies are related to additives such as benzene (2). In thepathology workers, there was not any hematologic disease. In some of the studies, cardiovasculerfindings such as palpitation and chest pain, hematologic findings such as decrease in leukocytenumber, deterioration in liver function tests, increase in urea level, renal effects such as distalrenal tubuler asidosis were found, but these were interpreted as changes that might be related toother chemicals contacted (16).

Prenatal Xy inhalation has been found to be embryotoxic and teratogenic (19, 20). Limitvalue for embryotropic effect is said to be 50 mg/m3 (20). Both Xy and FA are reported to causespontaneous abortus (21). It has been observed that in the persons contacted with Xy intake ofalcohol potentializes the toxic effect (22). It may cause blindness when there is contact with theeye, and should be treated as alkaline burns (23).

Although TLV-TWA value for Xy is 100 ppm, it should be kept in mind that this is theapproximate value suggested for the first 8 hours. It is mentioned that, the high concentrationencountered during the slide covering is temporary and there is no need for special ventilation, ifthere is no encounter with Xy in the other time periods in the 8-hour working time, and thatTLV-TWA level is not exceeded (24). In our department, Xy level was found 100 ppm during theslide covering, 74 ppm during the hematoxilen-eozin staining, 21 ppm during autotechniconsolution changing, and 22 ppm during histochemical staining (24). However, I personally believethat exposure should be minimized using all the possible precautions that could be taken, even ifTLV-TWA level is not exceeded.

Aromatic amines

All the stains used in pathology are dyes (light green, fast green, sudan IV, crystal violet,toluidine blue, etc. ) belonging to aromatic amines group. Aromatic amines are mostly related tobladder cancer, and risk is associated with exposure time and concentration. Potential risk forpathology is low (2). No increase in bladder cancer risk was observed in pathological studies (25).However, preventive measures must be taken when working with certain cancerogenic substancessuch as aldehyde fucsin and methyl violet used in PAS stain. It has been determined thatdiaminobenzidine used as a chromogen in immunohistochemistry is mutagenic and caused cancerin laboratory animals. However, it is noted that it should not be mixed up with benzidine which hascertainly a cancerogenic effect (2).

Other chemical substances

Methacrylate, used in plastic embedding and electron microscopy tissue blocking, is toxicand corrosive. When swallowed, inhaled or contacted, harmful effects are seen (2). It causescontact dermatitis through allergenic sensitivity, and may cause restrictive pulmonary syndromethrough respiration (26).

Gluteraldehyde used in fixation for electron microscopic examination is also used insterilization and disinfection. It has been started to be used to kill HIV (27). It causes rhinitis,asthma and contact dermatitis (28). No effect of it has been seen in pathology workers.

Picric acid used in Bouin fixation solution gains explosive character when dried. Silvercombined with ammonia also gains explosive character when dried. If crystalization or dryness isdetermined, they should be neutralized with NaCl solution first, and then disposed.

Latex

Latex and its derivatives that are in the structure of gloves cause contact dermatitis,rhinitis, conjuctivitis and asthma when reacted with IgE-mediated hypersensitivity. Effect of latexantigens inhaled in these circumstances is unknown (29, 30).

Physical damages

The most important of them is skin lesions done by cuttlers. Incisions and laserations aremostly seen in residents and technicians, and are directly proportional with work load (2). They areseen more in the hand that is not dominant. Real incidence is not known as no records are kept(31). It may cause failure in use of hand in acute period, and infections in chronic period. It hasbeen reported that v. cava filter mounted to prevent pulmonary embolism during the dissection ofan autopsy caused injury (32). It has been noted that implant cardioverter-defibrilator may causeelectric shock (33).

At a lower rate, fires and radiation are other physical accidents. Fire injury is generallyelectricty emanated. It is caused by tissue tracking apparatus where heat and solvents aretogether (34). Radiation injury is seen only in selective laboratories.

Microbiological risks

Agents most frequently encountered in pathology laboratories are hepatitis B and Cviruses, tuberculosis, and hydatid cyst agents. Apart from these, although rare, HIV (AIDS agent)and prions (mad cow disease agent) causes risk. Incidents causing occupational contact with theseagents are:

1. Breathing particules fumed from material by any means whatsoever,

2. Cutter and penetrative apparatus injuries (injection needle, suture needle, scalpel, etc.),

3. Contact of the agent to mucosa (eye, mouth, etc.) or to damaged skin.

Necessity to use cutter and penetrative apparatus in pathology practices generatespercutaneous contact risk. In a retrospective study done by O'Briain to determine the risk, 56% ofthe pathologists reported types of injuries of incision and needle sticking in one year (35). Wheninjuries were associated with work load, there was an injury in one in every 37 autopsies and 2629operation material examination. Residents reported injuries five times more than experiencedpathologists. 67% of the described injuries occured during dissection and in the distal part of thethumb, fore finger and middle finger which are used to hold the tissues opposite the dominanthand. Accidents in the form of injury/contact reported in this research occur because of;

* Incisions: knife, bone tip, microtome knife,

* Needle sticking: Covering the tip of the syringe, suture, bladder instrumentation,

* Blood and fluid splashes: Openning of cysts, dropping organs onto the dissection area.

In the prospective monitorings of the health workers who contacted HIV infected blood, HIVcontamination risk was found to be 0.3% in percutaneous injuries, and 0.09% in mucosalmembrane contact (36, 37). There is not sufficient information to determine the risk occuring aftercontact with other HIV infected body fluids and tissues. There are some factors affecting infectionrisk in prcutaneous injuries: amount of blood contaminating being large, HIV viral load being large.Injured person’s taking chemoprophylaxis decreases contamination risk.

In literature, among the health workers who were determined/found to have HIV contagionas a result of occupational contact, nurses come first. Only one pathologist who was contaminatedwith HIV through this way has been reported. In this case, injury causing the contamination wasdescribed as an incision with scalpel that caused too much bleeding in the pathologists’ hand whowas wearing double gloves during the autopsy of an AIDS patient (38).

The most risky material for HBV is, as in other agents, blood. The amount of virus in semenand saliva is 1,000-10,000 times greater than in blood. The amount of virus in urine and faeces isvery little if they are not contaminated with blood. The amount of blood to be inoculated from aninjury in the form of sticking a 22 gauge syringe is about 1 ml. There may be 100 infectious virionin this volume. HBV contamination risk in syringe sticking injuries is about 30% if the patient isHBeAg pozitive, and 6% if HBeAg negative. There may also be HBV contamination in the contactsrather than percutaneous injuries. What these kinds of contacts are not clear yet. Complying withthe general safety measures when working with human originated risky material, using barrier(gloves, etc.), HIV vaccination, and prophylaxsis greatly help occupational HIV contamination.Through these, the number of HIV contamination in the health workers in the USA decreased from17,000 in 1983 to 400 in 1995.

HCV in blood is found to be in much less titrates compared to HBV. Therefore, it is an agentthat generally contaminates as a result of contact with large amount of blood such as transfusion ofinfected blood and blood products. HCV contamination risk from an anti-HCV positive patientthrough needle sticking or cutter injury is about 1,8% (0-7%). In a study associating presence ofviremia and risk, the risk of HCV-RNA’s becoming positive in a health worker when contacted withan HCV-RNA positive blood through needle sticking was found to be 10% (39). No HCVcontamination through mucosa or healthy skin was not reported. However, there are two HCVcases occured with blood splashing to conjunctiva.

In terms of tuberculosis, health workers have 2-10 times higher risk compared to society(40). Bronchoscopy, transtracheal intubation and aspiration, abscess irrigation, and authopsy arerisk generating attempts for health workers (41). Whether diagnosed or not when alive,aerosolization formed during the autopsy of tuberculosis cases generates a risk for the people whoare present in the authopsy room. Because of a case who was given lung cancer diagnosis but wasactually tuberculosis infection, in 8 of the 55 (%14.5) health workers, among whom there werepathologists, PPD conversion was found; two of those health workers later developed activedisease (42). Another case reported in literature is a patient who was thought to have diedbecause of congestive cardiac failure and hepatic cirrhosis (43). In the autopsy of the case,pneumonia with extensive necrosis in lungs was found, tuberculosis infection (hematogenousspreading) in lungs, hiler lymph nodes, and in many other organs was diagnosed. No tuberculosisdevelopment in none of the 40 health workers who were in contact with the patient during the 21days of line in hospital was determined. However, from the 10 personnel in the autopsy room, inthe tracking of 5, who were known to be PPD negative, it was found that their skin tests hadbecome positive and M.tuberculosis was isolated from the phlegm of two. Small aerosols formduring the cutting of an infected lung or a bone (44). In this case, it was calculated that there wasone infectious particule in every 100 litres of the air in the autopsy room. This ratio is very highwhen compared to the information in the literature.

Cyst hydatid, apart from oral means, may cause disease by entering through mucosa oropen wound if splattered.

Prion diseases are a group of neurodegenerative disease that has been described inhumans and animals, and has fatal, contagious characteristic. It is also defined as contagious

spongioform ensefalopatiler (TSE) because in all of them vacuolization giving a “spongy”microscopic image in the substantia grisea of the brain has been determined. Studies to determineTSE agent make us think that a protein without nucleic acid is reponsible for it. Health workers arenot accepted as risk group, but TSE was determined in two brain surgeons, two histopathologytechnicians, and one pathologist (45, 46). There is no evidence to show a contamination frompatient in neither of these cases. Contaminaton via contact or air was not determined.Contamination as a result of percutaneous contact has been shown in test animals. Infectioncontamination to test animals from brain, spinal cord and CSF of prion infected humans andanimals has been determined (45). It has been accepted that precautions to be taken for AIDS orhepatitis cases would be enough also for prion patients (48). There is no risk in contact of patient’smaterial with healthy skin and mucosa membranes (except eye). Nevertheless, it is suggested toprevent direct contact with tissues that have high infectivity. Risk is higher in the case ofpercutaneous contact (wounded skin/mucosal membrane, eye, inoculation with cutters/perforators,etc.).

Ergonomic Risks

Pathology workers face muscle-skeletal system problems because of working in the samebody posture for long hours during the day. Although the number of studies on this matter islimited, in the results obtained, skeletal system problems especially in majority of microscopeusers were determined. In a study conducted in 1980 by Sodeberg et al., 84% of microscope usersreported muscle-skeletal system pains (49). In another study, constraint in seeing, waist pain,fibromialgy and stress headache in more than 80% of light microscope users were determined(50). Quitting work because of muscle-skeletal system problems in microscope users is reported tobe 19% in 1991 in the United States (51).

Because of the posture body takes when working in the same position, some parts areunder greater risk. Most risky regions are neck, back, waist, shoulders, elbows, wrists and fingers.One of the occupational safety and health, OSHA (Occupational Safety and Health Administration)reports that in microscope users, there are impacts in 50-60% neck, 65-70 % shoulders, 70-80%back, 65-70% waist, 40-60 % wrist, 25-35 % legs and feet (52).

Main reasons of the problems appear when working in pathology laboratory and atmicroscope are:

a- Working at static position: Human body has a structure that easily adapts to differentpostures and activities biomechanically. It works best by moving and changing position. Staticposture has as much risk as repetative motions. Muscles are designed to contract actively, andwhen they stay contracted blood circulation will be distorted. Staying in seated and bendedposition for long hours may cause exhaustion in muscles, and decrease in blood circulation becauseof insufficient pumping (53, 54).

b- Bad posture: Microscope, tissue inspection, and sampling taking necessitate working ina position bending forward with back and arms. Staying in this unnatural position causes cramps inmuscles, constrain in tendons and ligaments of neck, back, shoulders, arms and wrists (55).Frequently made posture mistakes are:

- Looking through microscope with neck flexioned forward

- Kyphotic inclination in back

- Protraction in shoulders

- Insufficient waist support of chair

- Insufficient forearm support (56).

c- Repetative activities: Repetetive activities done with fingers, and contact stress ofelbow on hard surface during the use of microscope, especially during focusing and scanning, maycause pain and nerve injuries, repetetive stress injuries and/or carpal tunnel syndrome (57).

d- Ergonomic deficiencies: If physical capacity of the worker and physical necessity ofthe working environment is incongruous, muscle-skeletal system problems may occur. There are

mostly carpal tunnel syndrome, tendinitis, waist pain, tiredness, stiffiness, pain, inflammationcomplaints in microscope users. The most risk bearing regions during microscope, gross inspection,and sampling are neck, back, shoulders, elbows, wrists, and fingers (58).

e- Lack of care: Most of the day time is passed in a non-statical posture (59).

f- Insufficient relaxing time: It has been reported that it is risky for the microscopeusers to work more than 5 hours a day; and 1-2 hours of microscoping is light work, 2-4 hours ismedium work, 4-6 hours is hard work, and more than 6 hours is very heavy work (54).

PRECAUTIONS

There must be written safety regulations in every laboratory. In these regulations;

*general safety

*contamination through blood

*international precautions

*basis for tuberculosis prevention

*accident communication and recording rules

*chemical hygene

*personal protective clothes and their uses

*fire and electricity safety

*ergonomic precautions

* use of harmful substances

-biological harmful substances,

-radioactive harmful substances,

-laser,

-chemical harmful substances,

-explosive liquids,

-flammable substances,

-carcinogenic substances,

-pressurized gases,

-ultraviolet,

-noise,

should be defined. Necessary precautiondsto decrease risks and to prevent accidents can berealized by an organization and training program with the participation of all individuals. The mainsubject of this program can be summarized as (60, 61):

1. determination and localization of risks,2. side effects of harmful substances, 3. principles of specimen processing, 4. storage of infectious material, 5. use of laboratory equipment, 6. use of cutters,

7. extermination of wastes, 8. fire precautions, 9. protection regulations.

A new technique or equipment that arrived to the unit should be introduced to all workers forthe purposes of adaptation and orientation. Within the framework of occupational health programs,training should be provided regarding ergonomic properties of the working environment, control oftechnical equipment, reports of diseases and accidents, general health controls, vaccination andimmunization. When establishing a new location, coordination between workers and planners isvery important. Co-decision is necessary when establishing ventilation, local stream removalsystems, safety cabinets (such as fume hood), access prevention and removal-extermination ofharmful substances, setting up electricity system, preservation of flammable liquids, and formingfire extinguishing system.

Things to be done in case of fire should be written and hanged in places easily visible. Use offire extinguishers should be taught to all personnel. Fire alarm, fire extinguishers, fire hose,fire-protective clothes, and asbest gloves should be available. Automatic watering system,fast-washing systems for kostic and toxic chemical substances, eye washing apparatus should betried to be obtained. Use of these equipment should be taught and their user guides should beprepared (62).

Laboratory clotthing should be water proof. They should be worn before entering the laboratoryand be taken off when leaving. Cleaning of these clothes are done by the employer. Gloves shouldbe protective, be taken off when telephoning, and be disposed after use. Hands should be washedfor 15 sec. every time gloves are changed. Daily clothes should cover whole body. Shoes shouldcover whole feet, canvas shoes should not be worn. Smoking, eating and drinking should not beallowed in the laboratory. Food and drinks should not be kept in the fridge. No make up should beallowed, long hair should be tied and covered. Hands should be kept away from hair, eyes, noseand face. There should be first aid kit in the laboratory. There should be “split-kit” of thesubstances used. Eye and face washing stations should be set up. There should be safety shower.There should be fume hood. Operation mask should be available. All broken, cracked glassequipment should be disposed.

Gloves should be worn when working with body fluids. Hands should be washed 15 secondsevery time gloves are changed. Protective-barrier clothes should be worn when there is a risk ofsplash. When there is splash, clothes should be changed immediatelly, splashed clothes should bedisinfected. These clothes should be changed when leaving the laboratory.

Risks in chemical substances are ranked between 1-4. If any of these ranks is 2 and above,there should be a diagram showing the risk on the box, and its meaning should be known (Picture2).

Picture 2: Diamond-shaped design showing risks in chemical substances, and their meanings.(upper section is red, lower white, left blue, and right yellow coloured)

Safety cabinets should provide 1-1.5 m3/min air flow. All electricity lines should beearthed. Equipment and glass apparatus should be immersed in disinfectant right after use (62).Loose gloves should not be worn when transferring liquid nitrogen into another container. Waistpart of the gloves should be fastened tightly if gloves are used. Container that nitrogen istransferred should be cooled before transfer. In a tightly closed container, liquid nitrogenevaporates and collected in the container. It should be kept in a ventilated container. Nitrogen tankshould not be kept in a room without ventilation. If flame burner is used in tissue inlay, it should beregularly maintained. There may be electricty conduction when tissues in paraffine bath are takenout. To prevent this, especially when working with old equipment, electricity should be turned offbefore taking out the tissues.

Ideal prevention in macroscopy hall benches and cytology processing benches, isventilation. Ventilation of the room with heated air provides air current in all areas (17). It shouldbe kept in mind that in places with general ventilation, mixing of FA or Xy with the system maycause mass damage that would affect whole hospital (17, 63). In local ventilation, it is important toknow the properties of the toxic steam. Xy is flammable and its density is 3,67. FA is a littleheavier than the air (d=1.07). It is ideal to do the elimination at a closest place to the source. It ismentioned that at specimen dissection bench, it is ideal to do water flow and steam aspirationtogether (2), a continuous water flow (also during the times when not working) is effective inelimination (17). Because of the flammable gases, aspired air should not contact the fan engine ofthe aspirator.

Specimens should be kept in closed containers that have holes on the lid for aeration, andcontainers should be stored in ventilated places. Especially maintenance of and solution changingin tissue tracking and staining equipment should be placed in an easily accessable fume hood orideally in a seperate ventilated room. Hand tissue tracking, staining, and covering should be donein fume hood. For lessening of Xy vapour, automatic covering equipment should be preffered ifpossible.

It is difficult, even impossible, to set up a new system in an already established laboratory.In the cases that these conditions cannot be provided, special filtrated cleaning equipment can beused. There are air cleaning equipment produced separately for FA and Xy to be used in pathologylaboratories (Surgipath Europe Ltd, UK; Thermoshandon, UK). Their prices are $1500-2000, andtheir filters are around $250-300. Peds designed to be used during the macroscopic processing ofautopsy or surgical specimens, elimination can be helped by preventing FA steam production.Assessing the smell in the room is sad to be enough to determine the changing time of the filters(4). Also, there are carbon filtered air cleaning equipment that can eliminate all harmful substances

(Thermoshandon, UK). While efficiency of carbon filter is high for many substances (15-20%), itshould be kept in mind that it is very low for FA (1-2%) (4). FA easily combines with urea andprecipitates, and urea or potassium permanganate is used in the filters of air cleaning equipmentand peds. If home production of such basic mechanismed products could be realized, it wouldbecome easier to reach every pathology laboratories. More detailed and technical informationregarding improvement of laboratory and macroscopy room conditions can be obtained fromrelated resources (17).

All working spaces except autopsy room of our department are in the same location andthey are conneceted to the general air condition system of the hospital. Staining, coverslipping andtissue processing equipment are in the same room. Cytology, tissue embedding and sectioning areperformed in one room, histochemical staining and immunohistochemistry are performed inanother room. There are also macroscopy, microscopy, slide archieve, researcher, lecturer, facultyrooms. 5 formaline cleaning equipment (Surgipath, Peterborough, UK) in the macroscopy room areleft working 24 hours. During the specimen dissection, specimens are placed on neutralizingbuffered ped, and are neutralized by pouring urea if formaline spills. Temporary storing ofspecimes is provided in the macroscopy room. Frozen equipment is also in the same room.Disposing process of the specimens is done in the autopsy room. In this environment outlinedbriefly, xylol and formaline levels have been measured under different conditions. Measurementswere taken at respiration level and for 8 hours or 15 minutes, and ready-made measurementboxes (monitoring badge) were used (Surgipath, UK). In this system, ready-made boxes are takenout of their package and attached to collar, put back into the package and sent to the firm after themeasurement, and measurement results are reported by the firm. In the measurements taken forformaline, it has been seen that the amount that persons not working with formaline directly(record and writing secretaries, routin technicians, sitology assisstants, lecturers, and faculty)wereexposed between 0.03-0.07 as TLV-TWA levels. The amount (TLV-TWA) that residents entrustedwith specimen dissection were exposed has been observed between 0.08-1.88. Residents wereexposed to (STEL value) 1.5 ppm formaline in 15 minutes while unloading specimens that retentionperiods were expired from the cupboard. During the disposal of specimens, dumping offormaldehyde in the container, retainer was exposed to 0.08 ppm formaline as TLV value, but realexposure level against time as TWA was 1,2 ppm, and when the formaline cleaning apparatus wasturned off, the TWA level increased to 1.88. In the measurements taken for xylol, persons notworking with xylol directly (tecnician, residents) were measured to be exposed to 2.73-3.92 ppm(TLV) xylol. The level technicians were exposed to during the changing of autotechnicon solutionswas 17.35 ppm as TLV, and 185.1 as STEL. Although there was an automatic covering equipment,covering was done by hand and STEL value for this process was found >300 ppm. During themicroscopic evaluation of frozen cross sections, dense xylol vapour coming out of the newlycovered preparate was measured and STEL value was found >300 ppm. When we look at thesemeasurements; 1. it can be seen that basic precautions are sufficient for formaline, tighterprecausons are needed during the disposal of specimens and dumping the formaline in containers,2. it stands out that there are serious problems as we do not have any precautions for xylol. Webelieve that these problems can partly be overcome by placing a xylol cleaning equipment into theequipment room. Real problem that draws attention is during the frozen evaluation. Obtained STELvalue (>300 ppm) is much higher than the permitted value of maximum 150 ppm. It shouldseriously be considered to evaluate frozens at a separate microscope with an accompanyingcleaning equipment next to it.

Surfaces in the autopsy room should be resistant to cuttings, and have easy-clean features.Different surface colours can be used to differentiate contaminated and non-contaminated. Thereshould be air conditioning. Air conditioned autopsy table is unnecessary. A different table ratherthan the autopsy table should be used for washing, dissection before and after fixation, and thereshould be air conditioning. Cutting skull with electrical saw causes dust and vacuum attachmentdoes not help it (64). Hand saw should be prefferred. Liquid aspirators used during autopsy anddissection should not be primitive, the quality of the ones used in surgeries should be preferred(64). The number of bacteria in the air is related to the number of people in the place and thierrate of motion. Because of that, there should not be unnecessary equipment and persons in theautopsy and dissection rooms (65). High-risk autopsies should especially be done with minimalnumber of persons. It is ideal to do it in an infectious diseases room, but if this is not possible, itcan be done in the same room (64, 66). All or some of the material such as water-proof cloth,plastic apron, surgeon mask, cap, water-proof shoes, glasses, gloves (kinds), allergen reactionprevention cream can be used during the autopsy and dissection of autopsy and surgical material.

Use of substances that can substitue harmful chemicals should be encouraged. Non-toxicvegetable oil instead of Xy (67); instead of FA, phenoxietanol in anatomy, 56% ethanol+20%

polyethylene glychol in pathology; in immunohistochemistry, instead of diaminobenzidine aschromogene, tetramethyl benzidine, 1-naftol basic dye, aminoethylcarbazole (AEC) or4-chloro-1-naftol; instead of latex gloves vinyl, neoprene or hypoallergenic latex gloves can beused (2). We know that there are laboratories in our country that uses alcohol in fixation. It is saidthat light microscopic properties are protected for many years with this fixation method. However,it causes contraction and crispiness in tissues. A fixative solution (StatFix) formed of 56% ethanol+ 20% polyethylenglycol + 4% glycerole + 17.5% buffer solution + 2.5% acetic acid is said todecrease the necessary fixative volume, shortened the staining time, eliminate the necessity ofepitope revealing processes for immunhistochemistry, be better suited for in situ hybridization andpolymerase chain reaction, but a few disadvantages of it are highlighted (68).

Gloves should be used to decrease the risk of contact with infectious material. Duringdissection, the most frequently injured region is the three fingers of the hand opposite the handthat does the cutting. It would be better to develop special protection methods for that region.Changing gloves and washing hands more often is a precaution that decreases risky contacts thatare caused by unnoticed glove punctures (69-71). In the needle sticking injuries, reaching theneedle to the skin by passing through the latex glove decreases inoculated blood amount 10 to 100times (72). Other barriers suggested to be used during the autopsy are eye glasses, surcical maskand cap, water proof apron, armlet and shoes (69).

Heavy work load and lack of experience increases the risk of injuries. It is appropriate toteach safety techniques at an early stage (35).

HBV vaccination is used to provide protection both before and after contact. After threedoses of intramusculer application, protective antibody response (10 mIU/mL) forms in > 90% ofhealthy individuals. Individuals who develop antibody response are protected against clinical andchronical disease risks. Studies have shown that immune memory formed by vaccination stays atleast 12 years even if anti-HBs level decreases (36). It is suggested that all health workers bevaccinated during their training or when starting their working life. In the workers who have a highrisk of HBV contact, it is suitable to apply anti-HBs response control 1-2 months after completingthree doses vaccination scheme. In individuals who have no response to vaccination, as they areopen to infection, hepatitis B immunglobuline prophylaxis should be applied after a risky injury.

Protective role of BCG is one of the issues that has been discussed for many years withoutany consensus. Meta-analysis of literature on this issue shows that BCG could suppresstuberculosis risk by about 50%, and prevents not primary infection but spreading of infection(menengitis, disseminal infection, etc.) (40, 44).

Disinfection

Resistance of microorganisms to disinfectants varies (Table 2).

Table 2: Resistance of microorganisms to disinfectants.

Highest resistance

Prions

Bacteria spors

Mycobacteria

Parasitic cysts

Encapsulated small viruses

Trophozoids

Gram negative bacteria

Fungi

Capsulated large viruses

Gram positive bacteria

Capsulated viruses

Lowest resistance

One of the disinfectants, glutaraldehyde is strongly effective against bacteria, fungi,viruses, and weakly effective against mycobacteria. 20-90 minutes of application has disinfectanteffect, 6-10 hours of application has sterilizing effect. Glutaraldehyde should be used inwell-ventilated medium. Formaldehyde is effective in all microorganisms. For optimal effect, 4%solution should be used for 24 hours. Sodium hypochloride (bleaching liquid) has sterilizing effect.The solution sold as bleaching liquid is a 5% solution. By 10 times diluting this, 0.5% solution isobtained. Diluting process should be fresh. As it is corrosive, it should not be used in surfaces. 70%alcohol is medium level disinfectant and has a rapid effect. Its effectivity against tuberculosis isabsolute. Although it is effective against bacteria, viruses and fungi, it does not generally killspors. Alcohol can not penetrate material that is rich in protein. Therefore, it may not be sufficientenough to clean surfaces contaminated with blood and bloody liquids with alcohol without apre-cleaning process.

Outer surfaces of sample containers should be cleaned with disinfectant before sending tothe laboratory. Containers of liquid samples should be put into liquid-proof bags after closing theirlids. Apparatus used in autopsy should be autoclaved after a suitable pre-cleaning or disinfection.Working surfaces and autopsy room floor should be washed and wiped after providing contact witha disinfectant (preferably sodium hypochloride) for 10 minutes. Fixation of tissues with formalinefor 24 hours is enough to kill all microorganisms except prions.

It is important to be careful about general precautions when working with fresh tissuessuch as frozen or autopsy. Hand saw should be used in cutting skull, high risk autopsies. Sprayshould not be used for freezing in frozen sectioning. Apparatus and equipment should beprocessed with suitable disinfectants if worked with infected or suspicious infected tissues.Fumigation is the most suitable method for frozen equipment. For this, 25 ml formaldehyde is putinto a container and heated with an electrical heater, or 25 ml formaldehyde and 10 g potassiumpermanganate are put into a container and left overnight. If potassium permanganate is addedmore it might explode, care should be given. Formaline steam should be cleared off. It should bekept in mind that the steam produced at that time is in large quantities (4). After that,formaldehyde should be neutralized by wiping with ammonia. Again, surfaces contacted withinfected blood, etc. should be disinfected with 5% bleaching liquid. When something spills, itshould be decontaminated with a substance special to that substance (“spill kit”, e.g. urea forformaline), then wiped with bleaching liquid. If the amount that spilled is large, sand or soil can be

used to take the excess. Inside of the equipment that could easily be infected, such ascytocentrifuge equipment, should be wiped with 2% glutaraldehyde.

Ventilation of the rooms (autopsy room) in those theer is a risk of bacteria carrying aerosolformation is important. There may be various methods to be applied. Using various methodstogether would increase safety.

a. Rooms with negative pressure, and air is changed at least 12 times an hour. It is veryexpensive to set up such systems. Effect of suggested air circulation rate to M.tuberculosiscontamination risk has not been investigated.

b. HEPA filtration system. HEPA filter is an air cleaning device that has been shown to beable to filter = 0.3 µm size particules in the air with 99.97% effectivity. It is used in the systemswhere air in the medium is filtered and given back to the medium, and in safety cabinets. It has tobe maintained regularly and changed according to rules when necessary.

c. Ultraviolet (UV) radiation. UV (253.7 nm) can be used in purification of medium’s airfrom infectious particules because of its anti-bacterial effect. Its contact with skin and eyes shouldbe prevented, bulb life should be monitored and cleaned regularly as dusty bulbs lose their effect.

d. Persons who are to be present in mediums where engineering measures are notsufficient may use masks in risky conditions. Masks that can be found commercially may havedifferent effects. Some of the properties that are important to look for when choosing a mask are:containing HEPA filter (or ability to filter 1 µm sized particules), adjustion to the face of the user,being easily cleanable, providing 50 L/minute air flow. Surgical masks to be used for this purpose isnot recommended. Surgical masks are for holding particules spreading from the users. They can beused only when suitable masks can not be found.

There should be a written plan regarding the method to be used after the contact withinfectious material. In this plan, there should be the unit/person that the contact would bereported, the way the risk would be evaluated, consultancy to be given to the person whocontacted, and information on prophylaxis and tracking after contact if necessary. Health workersshould be informed of this plan. Guidelines to be followed regarding this matter are:

1. As soon as the contact is realized, working should be stopped, contacted/injured regionshould be washed with plenty of water and soap. Treatment of the injury should be done using aniodine solution if necessary.

2. Serologic information related to HIV, HBV, HCV of the person whom the material thatcaused injury belongs should be reached and risk it carries in terms of these infections should betried to be determined with the help of epidemiologic and clinic information.

3. Serologic tests related to HIV, HBV, HCV of the injured health worker should be done. InHBV vaccinated persons, anti-HBs titration should be controlled and made sure to have a protectivevalue.

4. If the person that material belongs to is,

a. HIV positive: Risk arising as a result of the injury should be evaluated by a specialistphysician or team, chemoprophylaxis with reverse transcriptase inhibitors +/- proteaz inhibitorsshould be started if necessary (36). In a retrospective study, it has been determined that HIVseroconversion risk could be decreased about 80% by using zidovudine after a percutaneouscontact with HIV positive blood. Contamination causing viruses being resistant to the drug used,late start of chemoprophylaxis or continuing for insufficient period of time, some properties of hostor virus may result in unsuccessful prophylaxis. Serologic tracking of the injured person should bedone (for at least 6 months).

b. HBsAg positive: If the injured person is immune by natural infection or vaccination, thereis no need for an additional prevention. Hepatitis B immunglobuline and prophylaxis by vaccinationshould be applied to the persons who are at risk for infection. Prophylaxis should be startedimmediately after injury. Benefit of immunoprophylaxis applied after seven days is questionable(36).

c. HCV positive: There is no prophylactic agent that can be applied to prevent HCV infectionafter contact (36). It is suggested that the person be tracked at certain intervals with ALT and

anti-HCV for 6 months. Although there are people who suggest the application of alpha-interferonetreatment during acute HCV infection, it has not been proved to be more beneficial than thetreatment used in chronic infection.

d. If there is no serologic information for HIV, HBV, HCV: In terms of HBV, it is suggestedto take precautions as if contacted with an HBsAg positive material. Risk evaluation should bemade for HIV, decision should be made considering advantage and disadvantages of prophylaxisafter contact. There is no prophylactic prevention for HCV. Serologic tracking of the injured personshould be done for at least 6 months.

Prions are resistant to conventional inactivation methods because they do not containnucleic acid and have a different protein structure. X-rays, ultraviolet, boiling, formaldehydevapour, dry heat (Pasteur furnace), and chemicals (formaline, alcohols, gluteraldehyde,betapropiolactone) are ineffective (73, 74). Because of this, brain and other tissues fixated withformaline are accepted as infectious. Fixation with drying and alcohol, formaline, glutealdehydefixes ineffectivity and makes the sterilization difficult. For prion inactiation, autoclaving at 134 °Cfor 18 minutes and treat with NaOH provides the most effective result. For dry wastes, firstburning, if it is not possible, autoclaving at 134 °C for 18 minutes; and for liquid wastes, treatmentwith 1N NaOH (final concentration) or autoclaving at directed heat and time are suggested. Asformaldehyde vapour is ineffective on prions, wiping with first 1N NaOH, then 1N HCl followed bywashing with ater should be applied for the cleaning of safety cabinets. Microtome is cleaned withbleaching liquid or NaOH. There is no contamination from slides after coverslipping. However, if theslide is broken, it should be treated with bleaching liquid and then thrown away. Brain tissue couldbe fixed in formaline for 1-2 weeks. Tissue sections are left in 95-100% formic acid for 1 hour.They are fixated for 2 more days followed by tissue processing and embedding (48, 73-76).Althogh their effectivenesses have not been tested, there are some suggestions to decrease therisk that is present theoretically (73).

1. Contamination of healthy skin: Wash with plenty of water and soap. Do not damage theskin while washing. It can be suggested to contact the surface with 0.1 N NaOH or 1:10 dilutedbleaching liquid for 1 minute.

2. Contaminated needle sticking or laseration: Scarify the skin lightly and withoutdamaging. Wash with warm soapy water. Report the contact to the related section of yourinstitution.

3. Splashing to eye/mouth: Wash with plenty of water. Report the contact to the relatedsection of your institution.

4. Information regarding injury/contact should be kept for at least 20 years.

Ergonomy

Ergonomy is a branch of science that is interested in designing the work environment orwork in accordance with the capacity and limitations of human body. Ergonomy is adjusting workto worker. Conditions where there is incongruity between the physical necessities of work andphysical capacity of worker result in physical stress. Ergonomy aims at maximizing production andminimalizing physical and mental stress by optimizing the congruity between human andenvironment. Its benefits are:

Provides safe working opportunity (less injuries, safer working environment), Production increases, Quality increases, morale is boosted.

As ergonomic precautions, it is very important to keep spine in neutral position. Threecurvatures that the spine normally has should be kept while sitting. Instead of bending forward,position of the chair or table is adjusted. Chair is one of the important tools for a good ergonomicwork space. Supporting of chair of the body in a suitable form, and proper sitting position are veryimportant. Ergonomic designed adjustable chairs must be used. Back support of the chair shouldreach as far as below scapula, and its height and angle should be adjustable. Feet should be incontact with the floor. The most important part of the chair is the back support. Height of the chairshould be as low as providing waist to stay straight. Chair shold be moved towards table until waistis supported well. Most people work in hunchbacked position by keeping the chair high. Sitting at

this position for a long time causes strain in waist muscles. It is suggsted that first posture at thechair should be adjusted, then table height should be adjusted. Minimum requirements are:

a. Pneumatically adjustable height,

b. Adjustable sitting angle,

c. Adjustable back angle,

d. Adjustable back height (Upper part of the waist should be supported as much as thelower part),

e. Quality in cushion.

If feet are not contacted with floor after waist is supported with the back support of thechair, a small stool should be placed underneath the feet, otherwise venous return becomesdifficult. If femur length is not enough to support the back, back of the chair is bended forward or awaist cushion is used.

Time periods for work/rest should be appropriate. Short intervals are suggested to preventpostural and visual tiredness. Short, frequent intervals are more beneficial than long intervals. Thissaves the person from static posture. Stretching excercises can be done during these intervals.20-180 milliseconds micro-intervals can be taken in 10-15 minutes intervals. These are used notinstead of real intervals but to support them. Resting should be 15-30% of total working time.During that, posture and position changing, stretching excercises (Picture 3), and focusing eyes toa point at a distance are suggested to be done. (77-81).

Picture 3: Stretching excercises.

Conclusion

To summarize; acute FA exposure causes mucous membrane irritation, dermatitis anddecrease in pulmonary functions, and mutagenic effect and atopy in chronic exposure. It iscarcinogenic in high concentrations in animal experiments. There is no absolute data related tocarcinogenic effect in humans. Xy causes headache, nausea, coordination loss in low doses, andcentral nervous system depression and dermatitis with long term effect. It has embriotoxic andteratogenic effect in pregnants. It is observed that levels proposed for Xy are not exceeded, andfor FA, if efficient measures are not taken the level reaches to significant degrees in pathologylaboratories. Apart from FA and Xy, all chemicals used in histochemistry, immunohistochemistry orother special methods have similar harmful effects. Latex in gloves causes hypersensitivity.Physical damages such as cuttings appear as work loss and biological damages. Blood, body fluidsand aerosoles in breathing air carry infectious disease risk, and may cause serious diseases such ashepatitis, AIDS, tuberculosis. Working in the same position for a long time for both pathologytechnicians and pathologists bring about muscle and skeletal problems.

Safety and health of the workers are not a phenomenon that could be evaluated onlyeconomically. It is also expensive to provide bad working conditions Good spaces, equipment andtraining expenses are not more than bad ones. Workers are productive as long as they are healthyand professional. Health managers are responsible for establishing safe pathology laboratories thathave necessary equipment. Pathology workers should not accept less than necessary to providethese conditions.

Every laboratory should prepare written safety regulations in the frame of qualitycontrol/quality assurance, train its workers in safety, take necessary safety measures, hasnecessary safety facilities, and record and track accidents.

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