chemical safety and health conditions among hungarian hospital nurses

Chemical Safety and Health Conditionsamong Hungarian Hospital Nurses

ANNA TOMPA,a MATYAS JAKAB,b ANNA BIRO,b BALAZS MAGYAR,a

ZOLTAN FODOR,b TIBOR KLUPP,b AND JENO MAJORb

aDepartment of Public Health, Semmelweis University, 1096 Budapest, HungarybDepartment of Cytogenetics and Immunology, National Institute of ChemicalSafety, 1096 Budapest, Hungary

ABSTRACT: In the present study genotoxicological and immunotoxico-logical follow-up investigations were made on 811 donors including 94unexposed controls and 717 nurses with various working conditions fromdifferent hospitals (The Hungarian Nurse Study). The nurses were ex-posed to different chemicals: cytostatic drugs, anesthetic, and sterilizinggases, such as ethylene oxide (ETO) and formaldehyde. The measuredbiomarkers were: clinical laboratory routine tests, completed with geno-toxicological (chromosome aberrations [CA], sister chromatid exchange[SCE]), and immune-toxicological monitoring (ratio of lymphocyte sub-populations, lymphocyte activation markers, and leukocyte oxidativeburst). The highest rate of genotoxicologically affected donors (25.4%)was found in the group of cytostatic drug-exposed nurses. Comparinggeno- and immunotoxicological effect markers, we found that amonggenotoxicologically affected donors the frequency of helper T cell (Th)lymphocytes, the ratio of activated T and B cells increased, whereas theoxidative burst of leukocytes decreased. In hospitals with lack of protec-tive measures increased CA yields were observed compared to those withISO 9001 quality control or equivalent measures. Anemia, serum glucoselevel, thyroid dysfunctions, benign, and malignant tumors were more fre-quent in the exposed groups than in controls. The hygienic standard ofthe working environment is the basic risk factor for the vulnerability ofnurses. On the basis of these results, it is suggested, that the used cyto-genetic and immunological biomarkers are appropriate to detect earlysusceptibility to diseases. The Hungarian Nurse Study proved that theuse of safety measures could protect against occupational exposure atwork sites handling cytostatic drugs, anesthetic, and sterilizing gases.

KEYWORDS: cytostatics; anesthetics; sterilizing agents; chromosomeaberrations; sister chromatid exchange; unscheduled DNA synthesis;HPRT mutations; genotoxicological monitoring; immune toxicology; tu-mors; health status; risk assessment

Address for correspondence: Prof. Anna Tompa, M.D., Ph.D., Semmelweis University, Departmentof Public Health, P.O. Box 370, 1445 Budapest, Hungary.

e-mail: [email protected]

Ann. N.Y. Acad. Sci. 1076: 635–648 (2006). C© 2006 New York Academy of Sciences.doi: 10.1196/annals.1371.054

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636 ANNALS NEW YORK ACADEMY OF SCIENCES

INTRODUCTION

Occupational exposure to cytostatic drugs, anesthetic, and sterilizing gaseswith mutagenic and human carcinogenic capacity is a major hazard of thehealthcare personnel. The most effective means of minimalization of work siteexposures is the strict quality control (e.g., EU standard ISO 9001).1

In Hungary different recommendations have been published in order to re-duce the risk. Since 1994, guidelines addressing each step in the hazardousprocess of handling cytostatic drugs have been developed in Hungary in orderto decrease exposure and protect healthcare personnel, patients, and the envi-ronment. In 2000, Hungary conformed her legislation to the directives of theEuropean Union (67/548/EEC) by the Public Act No. XXV (2000) on Chem-ical Safety, and the 26/2000 order of the Ministry of Health on the protectionagainst occupational carcinogenic substances.1,2 In 2004, a methodologicalguideline of the National Institute of Pharmacy, Hungary on manufacturingand use of mixed cytostatic infusions was issued.3 The guidelines in theseregulations on the protection against exposure to carcinogenic agents and forthe performance of environmental and biological monitoring at workplaceswith higher cancer risk were largely based on previous results of the follow-up genotoxicology monitoring of nurses exposed to chemotherapeutic agents.These investigations were carried out by the Department of Genotoxicologyof the National Institute of Chemical Safety.

There was no publication of experimental or morbidity data combined withgenotoxicological monitoring before our study on the real risk of occupationaleffects induced by cytostatic, anesthetic, and sterilizing drugs on the nurse’shealth. Sporadic data without genotoxicological investigations are only avail-able on the odd ratios of the most characteristic symptoms as infertility, disor-ders in menstruation, hair loss, skin rush, and lightheadedness.4–6

An unusual cluster of breast cancer incidence appeared among nurses in theNewborn Unit of a county hospital in Northern Hungary in 1993. A cluster ofcancer cases, that is, eight breast cancers, two ovarian carcinomas as well asuterus, colon and brain tumors, and other malignant tumors occurred during theprevious 12 years (1981–1993) in the same Newborn Unit of the county hos-pital in Northern Hungary among the staff using an ethylene oxide (ETO) gassterilizer.7 The sterilizer was inappropriately repaired and run, consequentlyhigh ETO emissions occurred during sterilization. In addition the staff mem-bers of the unit were also exposed to low-level environmental radon. ETO is awell-known human carcinogen.8 ETO and ionizing radiation can increase bothchromosome aberration (CA) and sister chromatid exchange (SCE).8,9 CA andSCE frequencies were significantly higher in ETO and radon-exposed subjectscompared to that of sterilizing units in other hospitals.7 Formaldehyde, widelyused for sterilization, is also clastogenic.

In the last decades, a number of antineoplastic drugs have been introducedto the treatment of cancers. Most of these drugs however have been classified

TOMPA et al.: CHEMICAL SAFETY AMONG HUNGARIAN NURSES 637

to be carcinogenic to humans according to their mutagenic, clastogenic, andcarcinogenic properties.10–13 Since 1983, several guidelines for the handling ofanticancer drugs have been issued with the purpose of decreasing exposure andprotecting personnel.14 Occupational exposure of oncological nurses handlingneoplastic drugs may occur in different ways: by inhalation of airborne anti-neoplastic agents, absorption through skin contact, human excreta handling,ingestion during drug preparation and administration, and during disposal ofequipment.15,16

In the operation theaters the main genotoxicological hazard for the anesthe-siology personnel is the use of Halothane. A possible additional exposure mayoccur during the use of X ray for imaging.

The genotoxic effects of these agents underline the use of biomonitoringamong personnel with potential work site exposure. The evaluation of geno-toxic effects of occupational exposures to cytostatics is of primary interest inchemical safety and primary prevention. In biomonitoring studies of effectsin human populations exposed to genotoxic agents, cytogenetic methods withhuman peripheral blood lymphocytes (PBLs) have been extensively used.17

In lymphocytes of oncology nurses and pharmaceutists increased number ofCAs, SCEs, and gene mutations were found.18–22

Recognizing the hazardous effect of both cytostatic and gas-sterilizing agentson the health of nurses we have introduced a follow-up multiple end point geno-toxicological monitoring since 1992. The aim of our human genotoxicologymonitoring is to assess and minimize genotoxic risks and keep exposure as lowas possible. In the National Institute of Chemical Safety of Hungary, a multipleend point genotoxicology monitoring system has been developed since the mid1980s and was used for the risk assessment of different human populations,control subjects, and those occupationally exposed to various genotoxic agents.The monitoring is able to detect and follow-up the alterations in work-relatedconditions.23

The genotoxicological effect of chemical exposures detected in peripheralleukocytes raised the possibility of phenotypic and functional alterations inimmune-competent cells. Therefore in 2000 we were among the first to intro-duce the detection of immune-toxicological biomarkers to the genotoxicologi-cal monitoring system. Based on our previous experience, in the present studywe have chosen the ratio of lymphocyte subpopulations (T, helper T cell [Th],cytotoxic T cell [Tc], B, and natural killer [NK] cells), Th/Tc ratio, and theactivation (receptor for interleukin-2 [IL-2R] expression) of T cells as a meansof indicating immunological alteration.24,26 Donors were considered to haveimmune alterations if at least two of these parameters showed a considerabledifference compared to the normal range of values.

Here we present the results of the so-called Hungarian Nurse Study obtainedwith cytogenetic methods (CA and SCE) and immunotoxic investigations inthe examined groups of nurses preparing and/or handling cytostatic infusionsat the bedside, in nurses exposed to gas-sterilizing chemicals, for example,


formaldehyde and ETO, and in personnel exposed to different anesthetic gases.We also present the correlation between the observed biomarkers and the dis-ease burden of nurses.

MATERIALS AND METHODS

Donors and Sample Selection

Altogether 500 nurses (700 tests) handling cytostatic drugs, 86 nurses (117tests) exposed to sterilizing gases, 131 nurses (140 tests) exposed to anestheticgases collected during the whole study were investigated. In this study 92.1% ofthe investigated personnel were women. Results were compared to 94 healthy,age-matched controls (all women, working in medical care, but occupationallynot exposed to cytostatic drugs, sterilizing, or anesthetic gases). A total of 717exposed nurses were annually investigated for a period of 13 years, from 1992to 2004. The nurses were divided into subgroups according to the protectivemeasures used at the working place. The subgroups were: uncontrolled, whereno specific protection was used, controlled, where specific protective measureswere introduced, and quality controlled by the EU standard ISO 9001 (ISO).

Each donor was personally interviewed by filling in a routine questionnaireincluding demographic data, exposure and lifestyle (smoking and drinkinghabits), diseases, exposure to known or suspected mutagens, occupational his-tory including duration of exposure, and the use of protective devices duringwork. All retrospective medical records were available. Active smoker subjectswere considered “Smokers.” “Drinkers” consumed less than 80 g pure alcoholregularly (a liter of beer or equivalent) daily. Heavy drinkers were excluded.

Having the informed donors’ written permission, blood samples were col-lected from each donor by venipuncture. The samples were processed both forcytogenetic analysis and for routine clinical check-up including hematology,liver (SGOT, SGPT, and GGT enzymes), and kidney function tests as well asthe investigation of risk factors (i.e., serum glucose, serum cholesterol [totalhigh-density lipoprotein (HDL), and low-density lipoprotein (LDL)], triglyc-eride rate, and urine hyppuric acid concentrations), and for determination ofSCN levels as a marker of smoking.

Cytogenetic Analysis

Blood samples were processed for CA and SCE using standard cell cul-ture methods, which were identical in both protocols: 0.8 mL samplesof heparinized blood were cultured in duplicates in 10 mL RPMI-1640medium (Gibco) supplemented with 20% fetal calf serum (Flow) and 0.5%Phytohemagglutinin-P (Difco), without antibiotics; then 5 �g/mL 5-Bromo-2-deoxyuridine (BrdU, Sigma) was added at 22 h of incubation. For CA and


SCE analysis, the cultures were incubated at 37◦C, in the presence of 7% CO2,for 50 h and 72 h, respectively. Culture harvest, slide preparation,26 and stainingwere made following the standard methods using 5% Giemsa stain (Fluka) forCA, and according to the Fluorescent-Plus-Giemsa method for SCE.27 All mi-croscope analyses were performed on coded slides by the same (two) observers.Characterization of CA was performed according to Carrano and Natarajan28

in 100 metaphases per donor in the first mitotic cycle with 46 ± 1 chromo-somes. Mitoses containing only achromatic lesions (gaps) and/or aneuploidy(i.e., 46 ± 1 chromosomes per mitosis) were not considered aberrant. A totalof 50 of the second divisions per donor were scored for SCE.

Immune Phenotyping of PBLs by Flow Cytometry

Heparinized whole blood was mixed and incubated at room tempera-ture for 20 min with the appropriate amount of fluorescein-isothyocyanate-(FITC), phycoerythrin- (PE), peridinin chlorophyll protein- (PerCP), orallophycocyanin- (APC) labeled monoclonal antibodies against surface anti-gens. The erythrocytes were removed by lysis with the addition of fluorescent-activated cell sorting (FACS) Lysing solution (Becton Dickinson). After wash-ing with phosphate-buffered saline (PBS), samples were analyzed within 4 hafter labeling, or fixed with 2% paraformaldehyde. Four-color analysis wasperformed on a Becton Dickinson FACSCalibur flow cytometer. The studiedantigens were the following: CD3, CD4, CD8, CD14, CD19, CD25, CD45,CD56, and CD71. The monoclonal antibodies were purchased from BectonDickinson. Cell Quest Software 3.1 was used for analysis.

Measurement of Oxidative Burst Activity of Neutrophil Granulocytes

The measurement of oxidative burst was carried out from heparinized bloodsamples, using the Burst test (Phagoburst) kit, which uses the conversion ofdihydrorhodamine 123 to rhodamine 123 by reactive oxygen intermediatesproduced upon stimulation of neutrophil granulocytes. Cells were analyzed bya FACSCalibur flow cytometer. Cell Quest Pro Software was used for analysis.The mean fluorescence of rhodamine 123 correlates with oxidation quantityper individual leukocyte.

Statistical Analysis

Statistical analyses were performed by the Student’s t-test for CA, SCE;P < 0.05 was considered to be significant. The calculation of relative risk(RR) was based on the ratio of the incidence of exposed and nonexposedpersons.


RESULTS

In the present study we have examined altogether 811 donors between 1992and 2004. The subgroups according to working conditions and the numberof donors in each subgroup are summarized in TABLE 1. The demographicdata (mean age, percentage of smokers and drinkers) of the nurses and theunexposed subjects are presented in TABLE 2. All donors were in reproductiveage between 18 and 50 years.

Cytogenetic (CA and SCE) and immunology alterations in the first investi-gations of the follow-up study are presented in TABLE 3. In the “uncontrolled”subgroup of nurses exposed to cytostatics and anesthetics we observed signif-icantly increased frequency of CAs and SCEs compared to the unexposed. Asignificant increase in the mean SCE frequency was observed in nurses ex-posed to anesthetic gases and sterilizing agents, in the “uncontrolled” subgroupcompared to the “controlled.” However, both CAs and SCEs were significantlydecreased in the subgroup “ISO” compared both to “controlled” and “uncon-trolled.” Similar results in the cumulative mean CA frequencies could be ob-tained through the whole follow-up (TABLE 4) and in the first investigations ofthe study.

An increase of immune alterations occurred in all the investigated exposedgroups compared to the unexposed (TABLE 3). Immune alterations occurred innearly a third of the nurses exposed to sterilizing gases under controlled work-ing conditions. Among nurses exposed to anesthetic gases, the group workingunder controlled conditions was considerably less affected immunologicallythan the uncontrolled subgroup.

The comparison of gene- and immunotoxicological effect markers amongnurses exposed to cytostatics is shown in TABLE 5. The genotoxicologicallyaffected (CA > 4% and SCE > 7.5 per mitosis) donors showed an increase inthe frequency of Th lymphocytes, activated (IL-2R positive) T and Th cells,and transferrin receptor positive B cells. However, the frequency of NK cellsand the oxidative burst of leukocytes to opsonized Escherichia coli stimulusdecreased.

The most important biological, lifestyle, and exposure confounding factors,that is, age, smoking, drinking, and ionizing irradiation, were also investigated.

TABLE 1. The number of subjects and investigations in the subgroups of nurses accordingto protective measures during work

Exposure

Cytostatic drugs Sterilizing gases Anesthetic gases

Working environment Tests/cases

Uncontrolled 475/339 96/66 50/44Controlled 211/147 21/20 90/87ISO 14/14 — —


TABLE 2. Demographic data of nurses and unexposed controls

Average age Smokersa Drinkersb

Groups n (year ± SE) % %

Nonexposed (women) 94 39.9 ± 1.4 26.6 36.2Cytostatic drugs 500

Uncontrolled 339 34.2 ± 0.6 43.9 38.4Controlled 147 33.2 ± 0.7 43.5 49.0ISO 14 28.9 ± 2.1 42.9 85.7

Anesthetic gases 131Uncontrolled 44 40.9 ± 1.4 47.7 68.2Controlled 87 39.6 ± 1.0 33.3 63.2

Sterilizing gases 86Uncontrolled 66 42.3 ± 1.2 36.4 39.4Controlled 20 44.9 ± 2.4 20.0 45.0

aactive smokers.bless than 80 g pure alcohol regularly.

SCE values in smokers were significantly increased in all investigated sub-groups compared to nonsmokers (TABLE 6). In the subgroups exposed to anes-thetic and sterilizing gases, SCE was increased in the uncontrolled subgroupof nurses, compared to the controlled subgroup, regardless to smoking as aconfounding factor.

Some of the nurses were exposed not only to cytostatics, but also to ion-izing radiation (X ray and diagnostic and/or therapeutic radiochemicals).Other subgroups of nurses exposed to anesthetics and sterilizers were alsooccupationally exposed to X ray and ionizing alpha-radiation (environmental

TABLE 3. Cytogenetic and immune alteration data of nurses (first investigations of thefollow-up study)

CA SCE Immune% 1/mitoses alterations

Groups n (mean ± SE) (mean ± SE) %

Nonexposed 94 1.72 ± 0.25 6.44 ± 0.14 6.4Cytostatic drugs

Uncontrolled 339 2.32 ± 0.19a 6.57 ± 0.06b 9.9Controlled 147 1.77 ± 0.21 6.78 ± 0.09 12.5

ISO 14 0.79 ± 0.39a 6.20 ± 0.16b n.d.Anesthetic gases

Uncontrolled 44 1.45 ± 0.22 6.67 ± 0.16b 19.5Controlled 87 1.63 ± 0.20 6.24 ± 0.09 10.3Sterilizing gases

Uncontrolled 66 5.56 ± 0.68a 6.77 ± 0.14b n.d.Controlled 20 1.33 ± 0.36 6.08 ± 0.19 31.3

asignificant to the nonexposed, (Student’s t-test, P < 0.05).bSCE significant to the controlled (Student’s t-test, P < 0.05).n.d. = not determined.


TABLE 4. Cumulative structural CA frequencies (excluding gaps) in the exposed groups(all investigations)

Groups n CA % (mean ± SE)

Cytostatic drugsUncontrolled 475 2.50 ± 0.17Controlled 211 2.07 ± 0.20ISO 14 0.79 ± 0.39a

Anesthetic gasesUncontrolled 50 1.56 ± 0.23Controlled 90 1.62 ± 0.20

Sterilizing gasesUncontrolled 96 5.46 ± 0.47a

Controlled 21 1.26 ± 0.35

aSignificant in comparison to the controlled (Student’s t-test, P < 0.05).

radon exposure, in the case of ETO-exposed sterilizers only). Significant in-creases in mean CA and SCE were observed in donors exposed to cytostaticsand sterilizers with radiation, in comparison to the corresponding subgroupwithout radiation. Ionizing radiation also insignificantly increased the valuesof cytogenetic end points in case of exposure to anesthetic gases. The effect ofionizing radiation on CA and SCE in the exposed groups (all investigations)is shown in TABLE 7.

The clinical data and the incidence of different pathological conditions inthe exposed groups were compared to the unexposed group (TABLE 8). Therewas a considerable increase in the donor’s blood glucose level in the exposedin comparison to the unexposed. Similarly, the incidence of anemia, thyroidalterations, myoma, and other benign tumors in the unexposed group was low,whereas in the exposed groups it was increased.

In TABLE 9 the RRs of different diseases are summarized in the exposednurses.

TABLE 5. Comparison of gene- and immunotoxicological effect markers (nurses exposedto cytostatics)

Measured parameter Genotoxically nonaffected Genotoxically affected

Th (%) 43.79 ± 0.56 46.93 ± 0.90a

NK (%) 12.21 ± 0.43 10.67 ± 0.65a

Activated T cells (%)b 12.70 ± 0.78 16.30 ± 1.10a

Activated Th cells (%)b 18.53 ± 1.10 23.42 ± 1.10a

Activated B cells (%)c 40.78 ± 2.37 50.62 ± 3.57a

Oxidative burst (MFI)d 526.37 ± 32.67 334.74 ± 17.49a

aSignificant changes (Student’s t-test, P < 0.05).bAs measured by IL-2R expression.cAs measured by transferrin receptor expression.dMean fluorescence intensity.


TABLE 6. Comparison of the SCE results in smokers and nonsmokers

SCE 1/mitoses (mean ± SE)

Groups Smokers Nonsmokers

Cytostatic drugsUncontrolled 6.74 ± 0.08 6.38 ± 0.07Controlled 6.91 ± 0.11 6.59 ± 0.14ISO 6.54 ± 0.26 5.85 ± 0.10

Anesthetic gasesUncontrolled 6.92 ± 0.24 6.37 ± 0.18Controlled 6.44 ± 0.17 6.10 ± 0.08

Sterilizing gasesUncontrolled 6.96 ± 0.18 6.58 ± 0.20Controlled 6.55 ± 0.41 5.85 ± 0.18

The RR of thyroid alterations were increased in all exposed groups, whereasthe RR of breast and ovary cancer was only increased in nurses exposed tosterilizing gases. The RR of myoma was increased in all exposed groups, espe-cially in the subgroups exposed to sterilizing and anesthetic gases. Althoughthe incidence was increased in all exposed groups the RR of other benign tu-mors could not be calculated because their incidence was 0 in the unexposedgroup.

DISCUSSION

In the last two decades, several studies were published about the hazardsof handling cytostatic agents by health professionals, predominantly, among

TABLE 7. Ionizing radiation influencing CA and SCE in the exposed groups (all investi-gations)

CA SCE% 1/mitoses

Exposure n (mean ± SE) (mean ± SE)

Cytostatic drugsCytostatics 658 2.28 ± 0.13 6.69 ± 0.04Cytostatics + ionizing radiationa 42 3.21 ± 0.76c 7.08 ± 0.18c

Anesthetic gasesAnesthetics 62 1.47 ± 0.20 6.32 ± 0.10Anesthetics + ionizing radiationa 78 1.72 ± 0.22 6.50 ± 0.12

Sterilizing gasesETO 57 2.04 ± 0.30 6.31 ± 0.12

ETO + ionizing radiationb 60 7.07 ± 0.60 c 6.71 ± 0.16c

aWork site radiation (radioactive isotopes, X ray).bEnvironmental radiation (Radon).cSignificant changes (Student’s t-test, P < 0.05).


TABLE 8. Burden of chronic noninfectious diseases among hospital nurses

%

Cytostatic Anesthetic SterilizingDiseases Unexposed drugs gases gases

Increase in blood glucose level 21.3 33.8 30.53 31.4Anemia 8.5 11.8 16.79 10.47Metabolic-X syndrome 17.0 20.0 22.14 22.09Thyroid 1.1 9.2 9.16 8.14Breast + Ovary cc. 0.94 0.6 0.76 15.12Myoma 1.1 4.0 11.45 9.30Other benign tumors 0.0 8.4 8.40 12.79Allergy 45.7 35.2 45.80 39.5

nurses and pharmacists. It is difficult to provide definitive data on the type anddegree of risk for those exposed to chemotherapeutic agents.

A novel and promising approach to risk assessment is the use of immunetoxicological methods. Chemical exposure can alter the ratio of lymphocytesubpopulations and may cause changes in the activation of lymphocytes amongoil-industry, health-service, and metallurgy workers and thus specific immuno-logical markers can be monitored to assess exposure.24,25 In the HungarianNurse Study we have found an increase in immune alterations in all the ex-posed groups compared to the unexposed controls. In anesthetic-gas-exposednurses, the use of protective measures resulted in the decrease of immune alter-ations. In cytostatic-exposed nurses, the genotoxicologically affected donorsshowed an activation of lymphocytes, which we consider to be a consequenceof chemical exposure.25 However, the frequency of NK cells and the oxidativeburst of leukocytes to opsonized E. coli stimulus decreased, as a sign of thesuppression of innate immune responses.

In the present study we have carried out a multiple end point genotoxi-cology monitoring of the nurses exposed to cytostatics since 1992 in orderto follow-up the improvement in work-related conditions. Similarly, multiple

TABLE 9. RR of different clinical conditions among hospital nurses

RR

Diseases Cytostatic drugs Anesthetic gases Sterilizing gases

Increase in blood glucose level 1.6 1.4 1.5Anemia 1.4 2.0 1.2Metabolic-X syndrome 1.2 1.3 1.3Thyroid alterations 8.4 8.3 7.4Breast + Ovary cc. 0.6 0.8 16.1Myoma 3.6 10.4 8.5Allergy 0.8 1.0 0.9


end point genotoxicology monitoring was carried out among nurses exposedto sterilizing and anesthetic gases. In our study we have assessed the clini-cal changes and health condition of these groups, besides genotoxicologicaland immunotoxicological alterations. Some cytostatic and sterilizing drugs arecarcinogenic, mutagenic, or teratogenic, as it was well documented earlier inanimal experiments29–32 and some anesthetic gases were clastogenic in humanstudies.33,34

At the uncontrolled workplaces genotoxicological end points indicated occu-pational exposure to cytostatics13 and sterilizing gases. Exposure to Halothanealso increased CAs (data not shown) although the cytogenetic end points didnot indicate exposure to anesthetic gases in toto. Anesthetic gases, also harmfulto health, often do not cause increased levels of CA, however, SCE frequencieswere still increased significantly in an operating room personnel as compared tocontrols. Exposure to formaldehyde, as a sterilizing agent can cause increasedSCE among pathologists.35

The confounding effect of smoking, as a known SCE inducer36 cannot beexcluded in all the subgroups as SCE values in smokers were significantlyincreased in all investigated subgroups compared to nonsmokers. Cigarettesmoke, is similar to some environmental and occupational chemical pollu-tants. The confounding effect of smoking, as a known SCE inducer37 couldnot be excluded. SCE values in smokers were significantly increased in allinvestigated subgroups compared to nonsmokers. Environmental and occupa-tional chemical pollutants, for example, cigarette smoke, styrene, can also alterimmune functions.38,39

We also proved an additive effect between ionizing irradiation and ETOexposure in uncontrolled conditions.7,23 However, at all the controlled work-places the cytogenetic end points remained at the nonexposed control level,and a strict quality control according to ISO 9001 resulted in an even lowerCA yield corresponding to the healthy unexposed population.

Accounts have been reported of various acute symptoms experienced bynurses handling chemotherapy, such as hair loss, irregular menstrual cycle,and skin and eye irritation.4–6 We have also recorded these symptoms duringthe study. However, without safety regulations, nurses are more susceptibleto getting anemia, benign and malignant tumors, and thyroid dysfunctions(cf. TABLE 8). Improvements in working conditions have reduced the symp-toms of exposure to these chemicals. Regular clinical check-ups of the donorshave shown some differences in laboratory data between the exposed groups.Exposure to cytostatics, anesthetic, and sterilizing gases increase the risk ofthyroid alterations. Our investigation found an eight-fold increase in thyroidcomplaints caused by several pathological changes in the thyroid gland in allgroups of the exposed donors. Cancer of the thyroid gland was relatively rare,although the cancer of the breast and/or ovary was high in nurses exposed toETO, as we published earlier.7 Sterilizing gases, especially ETO may inducebreast and ovary cancer, whereas the risk of myoma is elevated in the case of


both anesthetic and sterilizing gases. Other benign tumors were increased inall exposed groups.

These results underline the importance of cancer education in medical staff.The total burden of cancer on the global community and the healthcare pro-fessionals is increasing; therefore cancer education must be an integral partof cancer prevention among students and nurses and among staff of oncol-ogy departments. Our study confirmed that the handling of chemotherapeuticagents gives a definite risk to healthcare professionals, highlighting that therisk is not restricted to neoplasms but extends to all chronic noninfectious dis-eases. Adequate education and training seems to be fundamental to provideinformation about risk reduction. The most important problem is changing thebeliefs, attitudes, and behavior of so-called “experienced” practitioners, whowere trained before the appearance of guidelines. The increased awareness andthe need for universal precautions in hazardous environments, like sterilizingunits, or anesthetic gas exposure, are necessary to solve this problem.

Hygienic conditions of the working environment are the basic risk factors forthe sensitivity of nurses to chemical agents. Cytogenetic and immunologicalbiomarkers are appropriate to detect early susceptibility to diseases. The Hun-garian Nurse Study proved that the use of safety measures could protect againstoccupational exposure at work sites handling cytostatic drugs, anesthetic, andsterilizing gases.

ACKNOWLEDGMENTS

The authors are thankful to Mrs. Iren Rethati, Mrs. Anna Herczeg, Ms.Andrea Toth, Mrs. Ildiko Bardi, Mrs. Eva Czifra, Mrs. Tunde Szeremlei-Szabone, Mrs. Andrea Hegedus, Mrs. Margit Tolyhi, and Mrs. ZsuzsannaSzep-Kis for the excellent technical help, and Dr. Edwin A. Konig in thecontribution of chromosome analysis. This work was supported by the grantsNKFP 1/016/2001 and NKFP 1/B-047/2004.

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chemical safety and health conditions among hungarian hospital nurses

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