Experiments with volunteers showed that 420% of an inhaled dose of vinyl chloride is retained in the lungs. This value is independent of the concentration of vinyl chloride in the air. Elimination of vinyl chloride through the lungs is negligible since its concentration in expired air decreases immediately after the cessation of exposuire.Interest in the toxic action of vinyl chloride (VC) has grown recently following the increased incidence of hepatic angiosarcoma found among VC polymerisation workers.In industry the main route of VC absorption is through the lung. No data on skin absorption in man are available, but it cannot be excluded since the compound was found to penetrate the skin of exposed monkeys.' The retention rate of VC in the lung was reported by Buchter et a12 to be 26-28 %, but these results were obtained from only two individuals exposed to 2-5 ppm VC and may thus be subject to error. The purpose of the present study was to determine the percentage retention of VC in the lung in man.Samples of inhaled air were collected into 500 cm3 gas pipettes every five minutes, the expired air was sampled using charcoal tubes, and four to five 10-minute samples were taken every hour. The VC concentration in both the inhaled and the expired air was determined by gas chromatography3; determinations were possible down to 0-3 mg/m3. The difference between the concentration in the inhaled and expired air was calculated to obtain the percentage retention of VC in the lung. Samples of exhaled air were also collected for the first 90 minutes after the cessation of exposure to determine the rate of elimination of VC from the lung. Results and discussion MethodFive healthy male volunteers aged from 26 to 31 were carefully examined by a doctor before and after exposure, and medical supervision was provided for each experiment. The volunteers were exposed to four atmospheric concentrations of VC with a 1 m3 toxicological chamber serving as the source of VCair mixtures. VC monomer from a pressure cylinder was mixed with precleaned air in a two-step flowdilution system to give the final concentrations. Volunteers were exposed for six hours to VC concentrations 60 mg/cm3 (24 ppm), 30 mg/cm3 (12 ppm), 15 mg/cm3 (6 ppm), and 7 5 mg/cm3 (3 ppm); values equal to 2, 1, 0 5, and 0-25 of the Polish maximum allowable concentration respectively. The subject remained outside the chamber and inhaled the air from inside through a gas mask connected with the interior of the chamber.

Three methods for desorption efficiencey determination were compared with a reference dynamic method for 12 compounds. Only one of them gave values that were statistically different. The method, in which standard solutions of determined compounds in CS2 are injected onto charcoal, is recommended to all laboratories dealing with air analysis as it is simpler than the dynamic method. Independence of the desorption efficiency on charcoal loading was also confirmed. The desorption efficiences for individual compounds and their mixtures were found to be different.

Enfl uran jest fl uorowanym anestetykiem wziewnym. Dane dotyczące działania enfl uranu uzyskano głównie od osób poddawanych narkozie. Minimalne stężenie enfl uranu w pęcherzykach płucnych w trakcie znieczulania, wyrażone jako procent atmosfery MAC (Minimal Anesthetic Concentration), wynosi dla osób dorosłych ok. 1,68% obj. U pacjentów obserwowano przypadki złośliwej hipertermii, niedociśnienie, depresję ośrodka oddechowego i niedotlenienie, zaburzenia rytmu serca oraz leukocytozę. Stwierdzano przypadki łagodnego i umiarkowanego uszkodzenia wątroby. Oszacowany próg obniżenia sprawności psychomotorycznej u ochotników narażonych na enfl uran z powietrzem wynosi 5% wartości MAC. Badania epidemiologiczne dotyczące narażenia zawodowego wzbudziły podejrzenie o wpływ mieszanin gazów znieczulających na częstość poronień, rozwój płodu, poród przedwczesny i wady wrodzone u dzieci, jednak w żadnym z tych badań nie określono szczegółowo rodzaju i stężenia stosowanych gazów znieczulających. W badaniu rakotwórczości i mutagenności dla enfl uranu uzyskano wyniki ujemne. Badania na zwierzętach obejmowały głównie narażenie na stężenia subanestetyczne enfl uranu. W większości doświadczeń nie znaleziono dowodów na zaburzenia płodności lub uszkodzenia płodu przez enfl uran u zwierząt. Skutkiem krytycznym działania enfl uranu u ludzi jest wpływ na ośrodkowy układ nerwowy, manifestujący się pogorszeniem sprawności psychomotorycznej. Do wyliczenia wartości NDS enfluranu wykorzystano wyniki badań na zwierzętach. Za wartość NOAEC dla działania układowego enfluranu przyjęto stężenie 153,2 mg/m3 (20 ppm), wyznaczone u szczurów (samców) narażanych na enfluran 8 h/dzień, 5 dni/tydzień łącznie przez 99 dni. Zaproponowano wartość NDS dla enfluranu na poziomie 38 mg/m3 (5 ppm). Zakres tematyczny artykułu obejmuje zagadnienia zdrowia oraz bezpieczeństwa i higieny środowiska pracy będące przedmiotem badań z zakresu nauk o zdrowiu i inżynierii środowiska.

StreszczenieW publikacji przedstawiono zasady organizowania i realizowania badań biegłości (proficiency testing -PT) w laboratoriach badania środowiska pracy oraz oceny i wykorzystania uzyskanych wyników z uwzględnieniem podstawowych wymagań zawartych w normach PN-EN ISO/IEC 17043 i ISO 13528. Podstawą prawidłowego funkcjonowania laboratorium badań środowiska pracy oraz gwarancją kompetencji i utrzymywania wysokiego poziomu jakości pomiarów czynników szkodliwych jest wdroże-nie i stosowanie skutecznego systemu organizacji, zarządzania i prowadzenia badań, np. według wytycznych opisanych w normie PN-EN ISO/IEC 17025. Potwierdzeniem kompetencji laboratorium do wykonywania określonych badań jest akredytacja. Istotnym narzędziem pomocnym w utrzymaniu kompetencji laboratorium -wykorzystywanym przez jednostkę akredytującą również w procesach akredytacji i nadzoru -jest udział w odpowiednim programie badania biegłości. W pracy omówiono rów-nież metody statystyczne niezbędne do oceny prawidłowego przygotowania obiektów do badania biegłości oraz wykorzystywanie tych metod do interpretacji wyników uzyskiwanych przez uczestników programu PT i oceny jakości wykonywanych przez nich badań. Med. Pr. 2016;67(2):267-283 Słowa kluczowe: badania biegłości, zapewnienie jakości, sterowanie jakością, system zarządzania, laboratoria badania środowiska pracy, programy badań biegłości AbstractThis publication presents the principles of organization, implementation, assessment and exploitation of proficiency testing results in the work environmental laboratory based on basic requirements included in standard PN-EN ISO/IEC 17043 and ISO 13528. The basis for the proper functioning of the laboratory is to use and observe the basic requirements for the competence to carry out the tests and the guidelines on ensuring reliable and accurate results, specified e.g., according to the guidelines described in the standard PN-EN ISO/IEC 17043. The confirmation of the laboratory competence is the obtained accreditation. To obtain this certificate several conditions, including proficiency testing (PT) should be met. The main aspects of this paper is to show the role of proficiency testing in the process of assuring a properly functioning quality system in the laboratory. The accreditation requirements, the types of proficiency testing schemes, methods of statistical analysis and interpretation of results are also discussed by the authors. Med Pr 2016;67(2):267-283Key words: proficiency testing, quality assurance, quality control, management system, industrial hygiene laboratories, proficiency testing schemes Autorka do korespondencji / Corresponding author: Agata Wziątek, Instytut Medycyny Pracy im. prof. J. Nofera, Zakład Bezpieczeństwa Chemicznego, ul. św. Teresy 8, 91-348 Łódź, e-mail: agata_wziatek@wp.pl Nadesłano: 25 sierpnia 2015, zatwierdzono: 28 października 2015 http://dx.doi.org/10.13075/mp.5893.00361 WPROWADZENIEPodstawą prawidłowego funkcjonowania laboratorium badań środowiska pracy oraz gwarancją utrzymywania wysokiego poziomu jakości p...

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.