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Doxorubicin (CAS: 23214-92-8) and its hydrochloride (CAS: 25136 40 9) are organic chemicals soluble in water. It is a cytostatic drug from the group of anthracycline antibiotics, used in antimitotic antitumor chemotherapy, primarily by intravenous, intravesical, and also in the case of lung cancer in the form of an aerosol for inhalation. In Poland, according to data from the Central Data Register on Exposure to Chemicals, Mixtures Thereof, Factors or Technological Processes with Carcinogenic or Mutagenic Effect, conducted at the Institute of Occupational Medicine in Łódź, the number of people exposed to doxorubicin and its hydrochloride in 2016 totaled 587. Administration of doxorubicin or its hydrochloride to patients at therapeutic doses may lead to myelosuppression, cardiomyopathy and myocardial fibrosis as well as neurotoxicity. Adverse effects of doxorubicin administration included cough, shortness of breath, chest pain, wheezing, hoarseness, hemoptysis, and bronchospasm. Systemic toxicity was defined as mild and transient and included sore throat, anorexia, dysgeusia, fatigue, nausea, tongue pain, tachycardia. Doxorubicin manufacturers state in their safety data sheets that inhalation of dust or aerosol is hazardous to health, may cause discomfort and nuisance, nausea, vomiting, bone marrow suppression, stomatitis, hair loss, and cardiotoxicity. Animal carcinogenicity studies have shown that doxorubicin was carcinogenic to rats after intravenous and subcutaneous administration, mainly causing mammary gland tumors. Doxorubicin has been shown to have genotoxic effects on somatic and embryonic mouse cells. Doxorubicin is toxic for reproduction. It may damage fertility and the unborn child. In Poland and in other countries, the highest permissible concentrations of doxorubicin and its hydrochloride in the work environment have not yet been determined. Occupational exposure limits are recommended by its manufacturers: FormuMax Scientific, Inc. and Pfizer at 0.0005 mg/m3. It was proposed to set up the MAC value for doxorubicin and its hydrochloride at the equivalent concentration level up to 0.1% of the lowest inhalational therapeutic dose found in the literature Dw = 0.04 mg/kg, i.e., 0.0003 mg/m3 – inhalable fraction. There are no substantive grounds to determine the STEL value. It is recommended to label the substance with the notation “skin” – the absorption of the substance through the skin may be just as important as when inhaled. The letters “Ft” should also be used – toxic for reproduction, Carc. 1B – carcinogen category 1B and Muta. 1B – germ cell mutagen category 1B. This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.

Ftalan dibutylu (DBP) jest stosowany jako dodatek zmiękczający do żywic i polimerów, a także środek żelujący, rozpuszczalnik, środek przeciwpieniący, przy wytwarzaniu farb nitrocelulozowych, włókien szklanych, kosmetyków, osłonek leków, insektycydów oraz środek smarny. W dostępnym piśmiennictwie dostępne są jedynie informacje dotyczące narażenia zawodowego na mieszaninę par i aerozoli plastyfikatorów ftalanowych. U mężczyzn narażonych na ftalany przy produkcji stwierdzono polineuropatie. Ftalan dibutylu jest zaklasyfikowany jako substancja działająca szkodliwie na rozrodczość kategorii zagrożenia 1B. Wartość LOAEL dla działania na rozrodczość manifestującego się istotnym i zależnym od dawki wzrostem częstości występowania morfologicznie nieprawidłowych plemników u szczurów, wynosi 31 mg/kg mc./dzień. Z kolei u myszy obserwowano zmniejszenie masy jąder, opóźnienie spermatogenezy oraz zaburzenia dojrzewania komórek Sertolego w wyniku narażenia na ftalan dibutylu w dawce ≥1 mg/kg mc./dzień. Za skutek krytyczny działania ftalanu dibutylu przyjęto działanie drażniące na drogi oddechowe oraz działanie na rozrodczość. Jako podstawę wyliczenia wartości NDS przyjęto wyniki 4-tygodniowego doświadczenia na szczurach. Za wartość NOAEC dla miejscowego działania drażniącego na drogi oddechowe przyjęto stężenie 1,18 mg/m3. Na podstawie przeprowadzonych obliczeń zaproponowano przyjąć stężenie 0,6 mg/m3 jako wartości NDS dla par i aerozoli ftalanu dibutylu. Nie ustalono wartości chwilowej, NDSCh.

Fluorouracil is a cytostatic drug used mainly in the treatment of gastrointestinal and skin cancers. It is usually used in a solution, in the form of an intravenous infusion or topically in a cream. The total daily dose of intravenous infusion is usually 12 ÷ 15 mg/kg bw./day, and a maintenance dose of 5 ÷ 10 mg/kg bw. The half-life of the drug is 8 ÷ 20 min. Its metabolism occurs mainly in the liver. The mechanism of action of fluorouracil is the inhibition of thymidine monophosphate biosynthesis, which leads to disruption of DNA replication and inhibition of tumor cell proliferation. Occupational exposure to fluorouracil occurs during its manufacture and packaging as well as the use of hospital wards in the daily treatment practice. Fluorouracil called Efudix is packaged in Poland at ICN Polfa Rzeszów S.A., Poland. Monographic studies for selected cytostatics for which there is exposure in Poland, such as methotrexate, cyclophosphamide, cisplatin, hydroxyurea, etoposide or fluorouracil are prepared at the request of the National Consultant in the field of nursing oncology in 2010 submitted to the Interdepartamental Commission on MAC and MAI. The application highlights the health risks for nurses employed in work with cytostatics, especially during their preparation and administration to patients. According to incomplete data, covering only 12 provinces, the number of nurses in oncology facilities amounted to a total of 5077, of which 215 had specialization in oncological nursing. In the 80s of the last century, fluorouracil was detected in the working environment of pharmacy technicians and nurses involved in the preparation of medicines. The maximum concentration of fluorouracil in the air was 82.26x10-6 mg/m3. Fluorouracil was detected on gloves, in the surfaces of the hospital: cabinets, floors, tables in the preparation room, door handles, internal fixtures, infusion bags and transport crates and transfer trays. Exposure tests of employees of pharmaceutical plants dealing in packaging and production of fluorouracil in 1986-1988, showed the presence of fluorouracil in the air of the working environment in concentrations up to 75 μg/m3 during product weighing operations. Exposure to fluorouracil was also monitored by determining the concentration of α-fluoro-β-alanine (FBAL), a fluorouracil metabolite in the urine of workers. The highest concentration of this metabolite was determined in the employee preparing the weight of the drug and it was 50 μg FBAL/780 ml of urine excreted between 10 and 13.75 hours after the start of the fluorouracil weighting. The main effects of fluorouracil toxicity are described in the treated patients. These included bone suppression and gastrointestinal toxicity. Topical application of solutions or creams containing 1-5% fluorouracil resulted in: skin irritation, dermatitis and allergic skin reactions. During the use of fluorouracil in the form of an aerosol in a patient at a therapeutic dose of 2.5 mg/kg/day, no effects on the systemic toxicity of the compound were observed. The patient was diagnosed with oral mucositis and glottis. Fluorouracil manufacturers in the safety data sheets indicate the possibility of health effects in workers including systemic effects after prolonged exposure through the respiratory tract and through the skin manifested by bone marrow suppression and cardiotoxic effects manifesting in ECG changes. The effects of exposure include: baldness, gastrointestinal symptoms, shortness of breath, convulsions, loss of consciousness, irritation of the skin, eyes and mucous membranes. These data have not been confirmed in reports or scientific publications. Several studies have found that the effects of cardiotoxic effects including blood pressure rise, as well as arrhythmia and cardiomyopathy, have been observed in medical personnel diagnosed with fluorouracil metabolite, ie α-fluoro-β-alanine, in the urine. Long-term effects of fluorouracil include mainly genotoxic effects found in oncological nurses and occurrence of birth defects in children of patients treated with this drug. In 27 nurses in two Portuguese hospitals an assessment of the risk of genotoxic activity using a micronucleus test was carried out. It was shown that the average incidence of micronuclei in peripheral blood lymphocyte cultures of nurses was significantly higher compared to the control. There have been reports describing the incidence of birth defects in children whose mothers were treated with fluorouracil during the first trimester of pregnancy, such as bone dysplasia, hypoplasia of the thoracic and abdominal organs. IARC experts in 1987 concluded that there was no evidence of carcinogenic effects of fluorouracil in humans and animals and they ranked it into group 3. In the case of animals, the dog was the most sensitive to fluorouracil. The minimum toxic dose for a dog after oral administration of fluorouracil was 5 mg/kg. and it was at the sustaining therapeutic dose level in humans. In a study on Syrian hamsters that were exposed to a fluorouracil aerosol (d = 2.5 μm) through the nose for 1 min, 3 times/wk, 5 weeks, at a dose of 1.45 mg/kg. and 2.08 mg/kg, no changes related to exposure were observed. The reprotoxic effect is the critical effect of fluorouracil in animals. The total fetal mortality was observed in Syrian hamsters, which were administered at a dose of 24 ÷ 75 mg/kg, while rodents had a teratogenic effect at a dose of 20 mg/kg. The drug in doses readily tolerated by mothers passed through the placenta in rats and caused increased resorption and mortality of the embryos. The fetal LD50 value of 5-flourouracil was 50 mg/kg, while the LD50 value for the mother was 230 mg/kg. In rats, the effects of teratogenic fluorouracil included, among others: cleft palate, micromithaphy, umbilical hernia. Occupational exposure levels were set by some of its producers and organizations only at the level of 0.001 ÷ 0.01 mg/m3. As a starting point for establishing OEL value of fluorouracil was proposed the concentration level equivalent to 0.1% of the smallest therapeutic dose, found in the human, ie. 5 mg/kg. An uncertainty factor "F" has been adopted at level 10 related to long-term effects of exposure, i.e. genotoxic and reprotoxic effects. MAC value of 0.0035 mg/m3 (inhalable fraction) has been proposed. There are no substantive grounds to determine the value of the maximum permissible temporary concentration (STEL). As an indicator of exposure to fluorouracil, the concentration of FBAL, metabolite in the urine was considered. The biological monitoring of exposure did not allow to obtain a relationship between the concentration of fluorouracil in the air and the concentration of FBAL in the urine. There is therefore no basis for determining the limit value in biological material (DSB). The authors of 8 out of 9 analyzed research reports recommend the use of the comet assay as a biomarker of the effects of exposure to cytostatics, including fluorouracil. Fluorouracil is absorbed through the skin. According to the criteria adopted by the Expert Panel on Chemical Factors, the term "skin" should be used - the absorption of substances through the skin may be as important as in the case of inhalation exposure, as follows: fluorouracil is classified by a consortium preparing joint submission of documentation registration for ECHA for acute dermal toxicity to hazard category 4; causes neurotoxicity in dogs and cats after application to the skin and is absorbed through the skin of patients being treated with a fluorouracil containing cream, causing side effects related to general organism toxicity of the substance. It should also be used with the letters "Ft" - a substance with reproductive toxicity. This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.

Cytostatics not only induce significant side-effects in patients treated oncologically but also pose a threat to the health of occupationally exposed healthcare workers: pharmacists, physicians, nurses and other personnel. Since the 1970s numerous reports from various countries have documented the contamination of working areas with cytostatics and the presence of drugs/metabolites in the urine or blood of healthcare employees, which directly indicates the occurrence of occupational exposure to these drugs. In Poland the significant scale of occupational exposure to cytostatics is also confirmed by the data collected in the central register of occupational carcinogens/mutagens kept by the Nofer Institute of Occupational Medicine. The assessment of occupational exposure to cytostatics and health risks constitutes employers' obligation. Unfortunately, the assessment of occupational risk resulting from exposure to cytostatics raises a number of concerns. Provisions governing the problem of workers' health protection are not unequivocal because they derive from a variety of law areas, especially in a matter of hazard classification and safety data sheets for cytostatics. Moreover, no legally binding occupational exposure limits have been set for cytostatics or their active compounds, and analytical methods for these substances airborne and biological concentrations are lacking. Consequently, the correct assessment of occupational exposure to cytostatics, the evaluation of health hazards and the development of the proper preventive strategy appear difficult. The authors of this article described and discussed the amendments to the European provisions concerning chemicals in the light of employers' obligations in the field of employees' heath protection against the consequences of exposure to cytostatics. Some modifications aimed at a more effective health protection of workers occupationally exposed to cytostatics were also proposed. Int J Occup Med Environ Health. 2019;32(2):141-59.

Over the past years, many legitimate concerns have been raised about the effects of dibutyl phthalate (DBP) as an endocrine disruptor, especially on reproduction. The aim of this publication is to critically review the literature related to the developmental and reproductive toxicity of DBP in animals. Several electronic databases were systematically searched until 2019. Studies were qualified for the review if they: linked exposure to DPB with reproduction, were published in English after 1990, and were conducted on animals. In the studies of the testicular effects of DBP on experimental animals, the most common effects of exposure included reduced fertility, atrophic changes in male gonads, degenerative changes in the epididymis, as well as a reduction in sperm count and motility, cryptorchidism, hypospadias, poor sperm quality and other genital defects (decreased testicular weight, delayed spermatogenesis, Leydig cell aggregation, impaired Sertoli cell maturation, and significant inhibitions of testicular enzymes). The embryotoxic effects of DBP on laboratory animals included mainly an increase in fetal resorption and a decrease in live births. The teratogenic effects of DBP also manifest as skeletal malformations in fetuses, malformations of male gonads and other genital effects. On the basis of the literature data, it is clearly demonstrated that DBP shows anti-androgenic effects; however, there are also reports confirming its weak estrogenic effect. Additionally, lower doses cause more adverse effects than the highest dose, which is an important fact because of the widespread environmental exposure to DBP. The studies clearly confirm that DBP is an endocrine disruptor. Int J Occup Med Environ Health. 2021;34(1):15-37.

Assessment of dermal exposure to chemicals in the work environment is problematic, mainly as a result of the lack of measurement data on occupational exposure to chemicals. Due to common prevalence of occupational skin exposure and its health consequences it is necessary to look for efficient solutions allowing for reliable exposure assessment. The aim of the study is to present predictive models used to assess non-measured dermal exposure, as well as to acquaint Polish users with the principles of the selected model functioning. This paper presents examples of models to assist the employer in the the assessment of occupational exposure associated with the skin contact with chemicals, developed in European Union (EU) countries, as well as in countries outside the EU. Based on the literature data dermal exposure models EASE (Estimation and Assessment of Substance Exposure), COSHH Essentials (Control of Substances Hazardous to Health Regulations), DREAM (Dermal Exposure Assessment Method), Stoffenmanager , ECETOC TRA (European Centre for Ecotoxicology and Toxicology of Chemicals Targeted Risk Assessment), MEASE (Metal's EASE), PHED (Pesticide Handlers Exposure Database), DERM (Dermal Exposure Ranking Method) and RISKOFDERM (Risk Assessment of Occupational Dermal Exposure to Chemicals) were briefly described. Moreover the characteristics of RISKOFDERM, guidelines for its use, information on input and output data were further detailed. Problem of full work shift dermal exposure assessment is described. An example of exposure assessment using RISKOFDERM and effectiveness evaluation to date were also presented. When no measurements are available, RISKOFDERM allows dermal exposure assessment and thus can improve the risk assessment quality and effectiveness of dermal risk management. Med Pr 2017;68(4):557-569.Ocena narażenia dermalnego na substancje chemiczne w środowisku pracy jest zagadnieniem problematycznym. Wynika to w pierwszej kolejności z braku danych na temat wielkości narażenia zawodowego, pochodzących z pomiarów stężeń chemikaliów. Ze względu na powszechność potencjalnego narażenia przez kontakt ze skórą w środowisku pracy i jego konsekwencje zdrowotne konieczne jest szukanie skutecznych rozwiązań umożliwiających wiarygodną ocenę narażenia. Celem pracy jest przybliżenie bezpomiarowej oceny narażenia dermalnego na substancje chemiczne za pomocą modeli predykcyjnych i bliższe przedstawienie zasad działania wybranego modelu polskim użytkownikom. W pracy przedstawiono przykładowe modele wspomagające pracodawcę w ocenie narażenia zawodowego związanego z kontaktem substancji chemicznych ze skórą pracownika, opracowane w krajach Unii Europejskiej, jak również poza Unią. Na podstawie danych literaturowych w artykule krótko opisano wybrane modele do szacowania narażenia dermalnego: EASE (Estimation and Assessment of Substance Exposure – oszacowanie i ocena narażenia na substancję), COSHH Essentials (Control of Substances Hazardous to Health Regulations – utrzymywanie pod kontrolą substancji niebezpiecznych dla zdrowia), DREAM (Dermal Exposure Assessment Method – metoda oceny narażenia dermalnego), Stoffenmanager, ECETOC TRA (European Centre for Ecotoxicology and Toxicology of Chemicals Targeted Risk Assessment – ukierunkowane szacowanie ryzyka Europejskiego Centrum ds. Ekotoksykologii i Toksykologii Chemikaliów), MEASE (Metal’s EASE), PHED (Pesticide Handlers Exposure Database – baza danych na temat narażenia użytkowników pestycydów), DERM (Dermal Exposure Ranking Method – metoda rankingu narażenia dermalnego) i RISKOFDERM (Risk Assessment of Occupational Dermal Exposure to Chemicals – ocena ryzyka wynikającego z narażenia dermalnego na chemikalia). Ponadto bardziej szczegółowo zaprezentowano charakterystykę modelu RISKOFDERM, wskazówki dotyczące korzystania z narzędzia oraz informacje na temat danych wejściowych i wyjściowych tego modelu. Opisano problem oceny narażenia dermalnego w ciągu całego dnia roboczego, a także przedstawiono przykładowe szacowanie narażenia za pomocą modelu RISKOFDERM i dotychczasową ocenę skuteczności tego modelu. W przypadku braku danych z pomiarów stężeń chemikaliów stwarzających zagrożenie dla pracownika w wyniku kontaktu ze skórą użycie modelu RISKOFDERM umożliwia ocenę potencjalnego dermalnego narażenia zawodowego, co może podnieść jakość oceny ryzyka, a przez to skuteczność sterowania ryzykiem wynikającym z narażenia przez skórę. Med. Pr. 2017;68(4):557–569.

Based on the literature, current legislation and the European Union (EU) directives, the rules to protect the health of workers in Poland and the countries of the former Eastern Bloc were analyzed. Since 2002, the activities in the field of hygiene standards in the countries of the former Eastern Bloc have been correlated with the EU policy. The functioning of the system of maximum admissible concentrations (MAC) having been implemented in Poland for many years before the accession to the EU, has provided for a relatively quick adjustment of Polish regulations on chemicals to the relevant European law. The Polish list includes 543 substances. In the former Eastern Bloc countries, intensification of work after joining the EU has caused the lists in those countries to contain from 285 substances in Slovakia to 780 in Lithuania. Currently, all substances included in the EU lists (up to and including the 3rd list of occupational exposure limit values of the Directive 2009/161/EC) have been governed by the Polish, Lithuanian, Czech, Latvian and Hungarian law. In Estonia and Slovakia the provisions of the Directive 2006/15/EC establishing the second list of occupational exposure limits have been implemented. Individual national lists contain much more chemicals than the EU list containing currently 122 substances. The legislative process in the EU is slow, and that is why the national law is important and necessary due to the local needs in selected areas. It is necessary to correlate the activities in the field of determining regional occupational exposure limit (OEL) values in the countries of the Eastern Bloc and the EU.W oparciu o dane literaturowe, aktualne akty prawne i dyrektywy Unii Europejskiej (UE) przedstawiono zasady ochrony zdrowia pracowników w Polsce i państwach dawnego bloku wschodniego. Od 2002 r. zadania w obszarze normatywów higienicznych w tych państwach są skorelowane z polityką UE. Funkcjonowanie w Polsce systemu ustalania wartości najwyższych dopuszczalnych stężeń (NDS) przez wiele lat przed wejściem do UE pozwoliło szybko dostosować polskie przepisy dotyczące chemikaliów do prawa europejskiego. Obecnie w polskim wykazie dopuszczalnych poziomów narażenia zawodowego znajdują się 543 substancje. W państwach byłego bloku wschodniego zintensyfikowanie prac nad ustaleniem tych poziomów po wejściu do UE spowodowało, że w wykazach tych państw znajduje się od 285 substancji (na Słowacji) do 780 (na Litwie). Obecnie wszystkie substancje w wykazach dopuszczalnych poziomów narażenia zawodowego w UE (do trzeciego wykazu wartości narażenia zawodowego opublikowanego w dyrektywie 2009161/EC włącznie) zostały wprowadzone do prawa polskiego, litewskiego, czeskiego, łotewskiego i węgierskiego. W innych państwach bloku wschodniego – Estonii i Słowacji – wdrożono przepisy dyrektywy 2006/15/WE ustanawiającej drugi wykaz wartości narażenia zawodowego w UE. Indywidualne wykazy krajowe zawierają znacznie więcej substancji niż wykaz UE (w którym są obecnie 122 substancje). Proces legislacyjny w UE jest powolny, dlatego wartości krajowe są ważne i potrzebne ze względu na lokalne potrzeby w wybranych dziedzinach i konieczność samodzielnych rozwiązań problemów. Niezbędne jest skorelowanie działań w zakresie ustalania regionalnych wartości dopuszczalnego narażenia zawodowego (occupational exposure limit – OEL) w krajach dawnego bloku wschodniego i w UE oraz wymiana informacji wynikających z przetworzenia olbrzymiej ilości danych literaturowych. Med. Pr. 2015;66(3):383–392.

The aim of this study was to assess the potential use of predictive models to estimate professional exposure to chemicals in the workplace, such as the operating room, by simultaneous determination of the levels of exposure using a model and measurements.Measurements included determinations of sevoflurane (SEV) in the workplace air of 117 operating rooms of 31 hospitals in one Polish region. Measurements were carried out at the time of various surgical procedures during administration of anaesthetics by endotracheal intubation. The measurement results were compared with the values estimated using two models: ECETOC TRA and Stoffenmanager.In one case the ECETOC TRA estimated the exposure concentration almost equal to the measured concentration but, because of the need to maintain a margin of safety in case of modelling, it can be concluded that the model underestimated the concentration. The Stoffenmanager model provided accurate exposure estimates in the examined case, and it can be used as a screening tool for the assessment of occupational inhalation exposure of medical personnel to anaesthetics.The results are of particular importance to the circumstances in Eastern Europe, where the levels of anaesthetics often exceed the relevant occupational exposure limits.

Jednym z najczęściej stosowanych leków cytostatycznych jest metotreksat (MTX) należący do antagonistów kwasu foliowego. Jest to substancja w Unii Europejskiej niezaklasyfikowana jako rakotwórcza, a Międzynarodowa Agencja Badań nad Rakiem (International Agency for Research on Cancer – IARC) oceniła, że nie ma dowodów na jej oddziaływanie rakotwórcze u ludzi i zwierząt. Mimo to MTX znalazł się na listach leków niebezpiecznych stosowanych w chemioterapii, głównie ze względu na właściwości genotoksyczne oraz działanie teratogenne, powodowanie toksyczności rozwojowej i szkodliwy wpływ na rozrodczość. Metotreksat wykryto w powietrzu oddziału szpitalnego podczas przygotowywania leku, na poziomie 0,3 μg/m3, a także na rękawicach ochronnych oraz czyszczonych powierzchniach pokoi przygotowawczych. Stężenie MTX na polietylenowym pokryciu wyciągu wentylacyjnego wynosiło 645 μg/m2. W większości prowadzonych projektów badawczych zidentyfikowano MTX w moczu pracowników opieki medycznej, farmaceutów i personelu pielęgniarskiego, a także pracowników służby zdrowia, którzy byli narażeni w wyniku wtórnego zanieczyszczenia powierzchni roboczych, odzieży czy pojemników. Najwyższe skumulowane stężenie MTX w 112 próbkach moczu wynosiło 1416 μg u pracowników podłączających i przygotowujących wlewy u pacjentów. Badania przeprowadzone w aptekach wykazały obecność MTX w 60% pobranych prób, a jego maksymalne stężenie wynosiło 15 ng/cm2 powierzchni tacy do odliczania tabletek. Dotychczas nie zostały ustalone obowiązujące prawnie wartości najwyższych dopuszczalnych stężeń (NDS) metotreksatu w środowisku pracy. Dopuszczalne poziomy narażenia zawodowego niektórzy producenci MTX ustalili w granicach 0,0003–0,0025 mg/m3. Naglącą potrzebą jest ustalenie wartości normatywnych. Należy podkreślić, że substancja wchłania się przez skórę, co może istotnie zwiększać narażenie, a pomiar jej stężenia w środowisku pracy może nie wystarczać do oszacowania rzeczywistego narażenia. Methotrexate (MTX) is one of the most widely used cytostatic drugs belonging to the folic acid antagonists. It is a substance non-classified as a carcinogen in the European Union and by the International Agency for Research on Cancer (IARC) as there is no evidence of its carcinogenicity to humans and animals. Nevertheless, MTX has been placed on the list of dangerous drugs used in chemotherapy, mainly due to genotoxic and teratogenic effects, causing developmental toxicity and reproductive toxicity. Methotrexate was determined in the hospital ward air during the preparation of a medicament at a level of 0.3 mg/m3, as well as on protective gloves and preparatory room surfaces. In most research projects MTX was identified in the urine of health care workers, pharmacists and nursing staff. The highest cumulative concentration of MTX in 112 urine samples was 1416 mg in workers preparing infusions for patients. Studies carried out in pharmacies revealed the presence of MTX in 60% of tests, and the maximum concentration of 15 ng/cm2 surface of the tray to count tablets. Legal exposure limit values for MTX in the work environment have not yet been established. Occupational exposure limits have been established by some manufacturers at the level of 0.0003–0.0025 mg/m3. There is an urgent need to establish normative values. It should also be emphasized that MTX is absorbed through the skin, which may significantly increase the exposure and measuring its concentration in the work environment may not be sufficient to estimate the actual exposure. praca przygotowana na podstawie wyników III etapu programu wieloletniego „Poprawa bezpieczeństwa i warunków pracy”, finansowanego w latach 2014–2016 w zakresie badań naukowych i prac rozwojowych ze środków Ministerstwa Nauki i Szkolnictwa Wyższego oraz Narodowego Centrum Badań i Rozwoju.

Aim: The aim of this study was to determine hydrogen sulphide concentration emitted from the mine extracting copper ore, to evaluate potential adverse health effects to the population living in four selected villages surrounding the exhaust shaft. Materials: Maximum measured concentration of hydrogen sulphide in the emitter is 286 µg/m3. Maximum emission calculated from the results of determinations of concentrations in the emitter is 0.44 kg/h. Results: In selected villages hydrogen sulphide at concentrations exceeding 4 µg/m3 was not detected in any of the 5-hour air samples. In all locations, the estimated maximum 1-hour concentrations of hydrogen sulphide were below 1 µg/m3, and the estimated mean annual concentrations were below 0.53 µg/m3. Conclusion: Any risk to the health of people in the selected area is not expected. As indicated by the available data on the threshold odour, the estimated concentrations of hydrogen sulphide may be sensed by humans.

The aim of this study was to develop an optimal strategy for the assessment of inhalation exposure to isocyanates such as TDI and MDI in the production of polyurethane foam by integration of theoretical and experimental data. ECETOC TRA and EASE predictive models were used to determine the estimated levels of exposure to isocyanates. The results of our study suggest that both applications EASE and ECETOC TRA can be used as a screening 1st Tier tool in this case study. PROC12 ECETOC TRA category can be linked to exposure on TDI during polyurethane foam manufacturing because it is working properly and exceeds 90th percentile measured concentration with factor 3 and the maximum measured value with factor 1, 5. The value estimated by using category PROC2 is underestimated so this category should not be linked to this scenario. At the same time, the applications of EASE overstate the expected concentrations although the scenario "Use in closed process" seems to underestimate the exposure at the "lower end". For MDI the both models estimate exposure in a conservative manner.

The aim of this work is to describe the operation principle of the TRA ECETOC model developed using the descriptor system, and the utilization of that model for assessment of inhalation exposures to different organic solvents for selected process categories identifying a given application.Measurement results were available for toluene, ethyl acetate and acetone in workplace atmosphere in Poland. The following process categories have been postulated: (1) Paints and lacquers factory: use in closed, continuous process with occasional controlled exposure; (2) Shoe factory: roller or brush application of glues; (3) Refinery: use in closed process, no likelihood of exposure. The next step was to calculate the workplace concentration at chosen process categories by applying the TRA ECETOC model.The selected categories do not precisely describe the studied applications. Very high concentration values of acetone were measured in the shoe factory, mean 443 ppm. The concentration obtained with the aid of the model is underestimated, ranging from 25.47 to 254.7 ppm, for the case with and without activation of the local exhaust ventilation (LEV), respectively. Estimated concentration at a level corresponding to that of the measured concentration would be possible if the process category involving spraying, e.g., PROC 7 was considered. For toluene and ethyl acetate, the measured concentrations are within the predicted ranges determined with the use of the model when we assume the concentration predicted with active ventilation for the beginning, and the concentration predicted with inactive ventilation for the end of the range.Model TRA ECETOC can be easily used to assess inhalation exposure at workplace. It has numerous advantages, its structure is clear, requires few data, is available free of charge. Selection of appropriate process categories related to the uses identified is guarantee of successful exposure assessment.

Based on the Estimation and Assessment of Substance Exposure (EASE) predictive model implemented into the European Union System for the Evaluation of Substances (EUSES 2.1.), the exposure to three chosen organic solvents: toluene, ethyl acetate and acetone was estimated and compared with the results of measurements in workplaces.Prior to validation, the EASE model was pretested using three exposure scenarios. The scenarios differed in the decision tree of pattern of use. Five substances were chosen for the test: 1,4-dioxane tert-methyl-butyl ether, diethylamine, 1,1,1-trichloroethane and bisphenol A. After testing the EASE model, the next step was the validation by estimating the exposure level and comparing it with the results of measurements in the workplace. We used the results of measurements of toluene, ethyl acetate and acetone concentrations in the work environment of a paint and lacquer factory, a shoe factory and a refinery. Three types of exposure scenarios, adaptable to the description of working conditions were chosen to estimate inhalation exposure.Comparison of calculated exposure to toluene, ethyl acetate and acetone with measurements in workplaces showed that model predictions are comparable with the measurement results. Only for low concentration ranges, the measured concentrations were higher than those predicted.EASE is a clear, consistent system, which can be successfully used as an additional component of inhalation exposure estimation. If the measurement data are available, they should be preferred to values estimated from models. In addition to inhalation exposure estimation, the EASE model makes it possible not only to assess exposure-related risk but also to predict workers' dermal exposure.

Our objectives included calculating the permeability coefficient and dermal penetration rates (flux value) for 112 chemicals with occupational exposure limits (OELs) according to the LFER (linear free-energy relationship) model developed using published methods. We also attempted to assign skin notations based on each chemical's molecular structure. There are many studies available where formulae for coefficients of permeability from saturated aqueous solutions (K(p)) have been related to physicochemical characteristics of chemicals. The LFER model is based on the solvation equation, which contains five main descriptors predicted from chemical structure: solute excess molar refractivity, dipolarity/polarisability, summation hydrogen bond acidity and basicity, and the McGowan characteristic volume. Descriptor values, available for about 5000 compounds in the Pharma Algorithms Database were used to calculate permeability coefficients. Dermal penetration rate was estimated as a ratio of permeability coefficient and concentration of chemical in saturated aqueous solution. Finally, estimated dermal penetration rates were used to assign the skin notation to chemicals. Defined critical fluxes defined from the literature were recommended as reference values for skin notation. The application of Abraham descriptors predicted from chemical structure and LFER analysis in calculation of permeability coefficients and flux values for chemicals with OELs was successful. Comparison of calculated K(p) values with data obtained earlier from other models showed that LFER predictions were comparable to those obtained by some previously published models, but the differences were much more significant for others. It seems reasonable to conclude that skin should not be characterised as a simple lipophilic barrier alone. Both lipophilic and polar pathways of permeation exist across the stratum corneum. It is feasible to predict skin notation on the basis of the LFER and other published models; from among 112 chemicals 94 (84%) should have the skin notation in the OEL list based on the LFER calculations. The skin notation had been estimated by other published models for almost 94% of the chemicals. Twenty-nine (25.8%) chemicals were identified to have significant absorption and 65 (58%) the potential for dermal toxicity. We found major differences between alternative published analytical models and their ability to determine whether particular chemicals were potentially dermotoxic.

Derived No Effect Level (DNEL(inh)) has been set for occupational exposure to but-2-yno-1,4-diol according to REACH principles. Maximum allowable concentration (MAC) and DNEL(inh) have been compared.Experimental data from two inhalation studies on rats and three oral studies have been used to calculate DNEL.Estimated DNEL(inh) values show significant differences and fall within the range of 0.33-0.02 mg/m3, depending on the chosen experiment and critical effect. It seems that a 30-day inhalation study best reflects the penetration of xenobiotic to the human organism. This experiment has been used to set MAC value of but-2-yno-1,4-diol of 0,25 mg/m3 and it is close to local DNEL(inh)--0.10 mg/m3. Both values have been estimated on the same starting point NOAEC(loc)--0.5 mg/m3, but different assessment factors have been applied.A general feeling is that because of the differences in methodologies for calculating DNELs versus those used for calculating health-based OELs, the DNEL will tend to be lower than any corresponding health-based OEL for that chemical. This indicates that the OEL does not provide the appropriate level of protection required by REACH. The calculation leads to a new value (DNEL) that requires different risk management measures and operational conditions.

In 2007, a new maximum admissible concentration value of 88 mg/m3 was specified for dichloromethane (DCM) in the Polish list of admissible concentrations of harmful chemicals and dusts in the work environment atmosphere. The new value is four times higher than the former one (20 mg/m3), valid in Poland for 20 past years. At the same time, it was decided that the value of short term exposure limit (STEL) shall no longer be specified. Dichloromethane is a chemical which can be absorbed by routes other than respiratory, therefore, biological monitoring is required to ensure that the risk is not underestimated. Experimental data support the conclusion that volatile chloroorganic compounds, including dichloromethane, are excreted with urine in the unchanged form, and thus their absorption and exposure can be easily assessed. Concentration of dichloromethane in urine determined at the end of work shift is proposed in Poland as a specific index of dichloromethane exposure. Dichloromethane inhalation exposure at maximum admissible concentration of 88 mg/m3 corresponds with biological exposure index (BEI) of 0.15 mg DCM/l urine. The BEI value proposed in Poland for DCM is compatible with that specified by the American Conference of Governmental Industrial Hygienists (ACGIH).

In 2004, the category of formaldehyde carcinogenicity was changed in Poland so that it is now coherent with the requirements of the European Union classification of carcinogenicity. Formaldehyde was categorized into group 3 as the substance not classifiable as to its carcinogenecity to humans because the collected information was not adequate for making a satisfactory assessment. There is some evidence from appropriate animal studies, but it is insufficient to categorize this substance in group 2: probably carcinogenic to humans. In 2006, the International Agency for Research on Cancer categorized formaldehyde in group 1 as the substance carcinogenic to humans. Three types of cancer were assessed: nasopharyngeal cancer, leukemia and sinonasal cancer. There was sufficient evidence that formaldehyde causes nasopharyngeal cancer, strong but not sufficient evidence that the substance induces leukemia and limited evidence for sinonasal cancer. Based on the irritation effect, the value of maximum admissible concentration of formaldehyde in the work environment has been established in Poland at 0.5 mg/m3 as average weighed concentration, and 1 mg/m3 as short-term concentration. In the European Union, the values of 0.2 ppm and 0.4 ppm, respectively are now being considered. It is assumed that the MAC value for formaldehyde in the work environment will be soon verified in Poland and adapted to European Union standards.

Dichloromethane (DCM) has been widely used in Poland and worldwide as a pesticide fumigant to preserve seed and fruit, in the manufacture of polyurethane, in the cosmetic, pharmaceutical and food-processing industry. It isalso used as an ingredient of fire extinguishing formulations and as a cooling agent in refrigerators. Because of dichloromethane's widespread use, its multisystemic toxic activity and a significant number of the exposed people, it is important to assess occupational risk for dichloromethane. In Poland, the maximum admissible concentration of dichloromethane based on its carcinogenic effect is MAC TWA 20 mg/m3 and MAC STEL 50 mg/m3. However, according to experimental and epidemiological data, occupational risk associated with DCM use is attributable to its effect on central nervous system rather than to its carcinogenic activity.

Sevoflurane and isoflurane are polyfluorinated anesthetics used during surgical treatment of both adults and children. They are usually applied as mixtures with oxygen or dinitrogen monoxide. An assessment of health risk of exposure to these inhalant anesthetics poses a serious problem for employers, mostly due to the fact that maximum admissible concentrations (MAC) for these compounds have not been established. Consequently, there is no obligation to measure their air concentration in the workplace. However, the employer is responsible for determining whether or not a given hazardous agent is present in the work environment. The setting of MAC values for sevoflurane and isoflurane has recently been considered by the Expert Group for Chemical Hazards that proposed to accept 55 mg/m3 (7 ppm) and 32 mg/m3 (4 ppm), respectively as MAC values in assessing workplace hazards. These exposure levels should protect the surgical staff from adverse neurological, cardiovascular, respiratory, and irritant effects.

The European Union has published a list of dangerous chemicals, along with classification and labeling; in 1997 the list was adapted to the requirements of Polish regulations and has been continuously updated since then. We have decided to adopt data on dangerous chemicals classification in the list referring to their dermal absorption to assess whether the skin notation is required in the maximum admissible concentration (MAC) list. In Poland, the Group of Experts for Chemical Agents (GECA) decides on assigning the skin absorption notation (symbol Sk) when analyzing the literature data collected in order to prepare occupational exposure limits documentation. The LD50s value serves as the main criterion for assigning the notation. The limit value of 1000 mg/kg has been set as the criterion for applying the skin notation. Documented results of animal and human research, which point to systemic effects resulting from dermal exposure and physicochemical characteristics enabling calculation of the dermal absorption rate may also be used as the basis for assigning the skin notation. Chemicals for which GECA recommended using the skin notation in the 2004 MAC list have been analyzed. It was concluded that information on the classification of chemicals in the list of dangerous chemicals is useful for assessing the skin absorption, but quantitative assessment of absorption rate compared to "safe" levels, using the available theoretical models, should also be attempted.

In 2002, it was necessary to harmonize Polish law on admissible limits of occupational exposure with EU requirements. To this end, the Expert Group on Chemical Agents proposed maximum admissible concentration values for 29 chemicals: acrylaldehyde (107-02-8); cresols, mix of isomers (95-48-7), 108-39-4, 106-44-5, 1319-77-3); tetraphosphorus decaoxide (1314-56-3); ethylamine (75-04-7); naphtalene (91-20-3); nitrobenzene (98-95-3); nitrogen oxide (110-54-5); nitrogen dioxide (10102-44-0); pyridine (110-86-1); butan-2-one (78-93-3); carbon oxide (630-08-0); 1,4-dichlorobenzene (106-46-7); 1,2-dichlorobenzene (95-50-1); hexane (110-54-5); aluminum hydroxide (21645-51-2); aluminum (fumes and dusts) (7429-90-5); amitrole (61-82-5); 2,2-bis(4-hydroxyphenyl)propane (bisphenol A) (80-05-7); 3a,4,7,7a-terahydro-4,7-metanoindene (dicyclopentadiene) (77-73-6); trimethoxyphosphane (121-45-9); methyl chloroacetate (96-34-4); 4-methoxyphenol (150-76-5); methyl formate (107-31-3); 2-phenoxyethanol (122-99-6); divinylbenzene (1321-74-0); Diesel exhausts (-); hexane-6-lactam (dusts and fumes) (105-60-2); 2-isopropoxyethanol (109-59-1); and methyl 2-cyanoacrylate (137-05-3).