PRINCIPLES AND METHODS OF ASSESSING THE WORKING ENVIRONMENT

NUMBER 2 (100) 2019




  • ISO 21083 − new international standard for determination of nanoparticles filtration efficiency
    dr inż. Szymon Jakubiak, p. 7-11
  • Etoposide – inhalable fraction. Documentation of proposed values of occupational exposure limits (OELs)
    dr Renata Soćko, p. 19-47
  • Fluorouracil − inhalable fraction. Documentation of proposed values of occupational exposure limits (OELs)
    mgr inż. Małgorzata Kupczewska-Dobecka, p. 49-81
  • 2-Nitroanisole. Documentation of occupational exposure limits (OELs)
    prof. dr hab. Andrzej Starek, p. 83-99
  • Zinc dichloride. Determination in workplace air
    mgr Jolanta Surgiewicz, p. 101-112
  • 3,3’-Dimethoxybenzidine. Determination in workplace air
    dr Joanna Kowalska, dr inż. Anna Jeżewska, p. 113-125
  • Dimethyl phthalate. Determination in workplace air
    inż. Agnieszka Woźnica, p. 127-137
  • Calcium hydroxid. Determination in workplace air
    mgr Jolanta Surgiewicz, p. 139-150
  • ISO 21083 − new international standard for determination of nanoparticles filtration efficiency
    dr inż. Szymon Jakubiak

    The new international standard ISO 21083 provides a method of testing filter media during the filtration of spherical shaped nanoparticles. The described procedure can be used to determine operating parameters of filtration materials of any classes. The filtration efficiency is determined on the basis of averaged results obtained for samples of the tested ma­terial in the initial state and after neutralization of the charge in the 2-propanol vapour. The standard does not introduce a division into filter classes, and in the final report of the tests, fractional particle retention efficiencies are given. This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



    Etoposide – inhalable fraction. Documentation of proposed values of occupational exposure limits (OELs)
    dr Renata Soćko

    Etoposide at room temperature is a solid present in the form of a white or yellow-brown crystalline powder. It is an anticancer drug with cytotoxic and anti-mitotic activity, used to treat patients with testicular cancer, acute myel­ogenous leukemia, lung cancer, non-small-cell lung cancer, adrenal cortex cancer, gastric cancer, hepatoblastoma, acute lymphoblastic leukemia and brain tumors. It is also recommended for the treatment of Ewing sarcoma and Kaposi’s sarcoma associated with AIDS. This cytostatic is available in capsules taken with food and in a concentrate for a solution for infusion. Occupational exposure to etoposide occurs during its manufacture, confectioning, packaging and use in everyday treatment practices of hospital wards. The monograph, along with the proposal for a hygiene standard for etoposide, was developed as a continuation of work on the determination of the value of hygiene stan­dards for cytostatics. According to the report of the National Consultant in the field of nursing in 2010 (incomplete data, covering only 12 voivodeships), in total 5077 nurses were employed in oncology facilities. On the basis of data from the Central Register of Data on Exposure to Carcinogenic or Mutagenic Substances, Mixtures, Agents or Tech­nological Processes in Poland exposure to etoposide in Poland in the last three years has been growing. In 2015, 414 people were exposed to the substance. This substance has not been officially classified in the European Union. Most manufacturers of etoposide importers classify it for carcinogenic activity as category 1B with the following phrase on risk: May cause cancer and acute toxicity after oral exposure to category 4. The main effect of the toxicity of etoposide as a medicine is suppression of bone marrow function, which results in neutropenia, granulocytopenia and throm­bocytopenia, leukopenia, an increase in the number of megaloblasts in bone marrow and gastrointestinal symptoms (e.g., nausea, vomiting with mild to moderate intensity), bronchospasm, inflammation of mucous membranes, feelings of disgust in the mouth, baldness and secondary leukemia. According to the IARC, there is limited evidence of car­cinogenicity of etoposide in animals, but there is sufficient evidence of carcinogenicity of etoposide in humans when there is combined exposure to cisplatin and bleomycin. In IARC, etoposide was classified as probably carcinogenic to humans (Group 2A), and in combination with cisplatin and bleomycin as a carcinogen for humans (Group 1). The genotoxic activity of etoposide has been demonstrated in studies performed on human and animal material in vitro without metabolic activation. Etoposide caused the occurrence of chromosomal aberrations in both humans and lab­oratory animals, increased sister chromatid exchange, double-strand break in DNA and the micronucleus formation. In laboratory animal studies (mice, rats, rabbits), etoposide was teratogenic and embryotoxic. In women treated with etoposide, transient ovarian dysfunction was reported. The effect of etoposide on ovarian function, however, did not depend on the dose, but on the patient’s age. In addition, spontaneous births were reported in women treated with etoposide. In some cases, the embryotoxic effects of the drug have been demonstrated. There were no congenital malformations in children whose mothers were treated with etoposide alone or in combination with other cytostatics, as well as in children of men treated with etoposide. The critical effect of the action of etoposide as a drug is bone marrow suppression. The lowest therapeutic dose of the drug was found at 2.37 mg/kg/day. In Poland, the maximum permis­sible concentrations (MAC) of etoposide in the work environment have not yet been established. The following data were taken into account when determining the MAC of etoposide:

    − occupational exposure levels established by etoposide manufacturers for this substance amount to 0.0003 or 0.0007 mg/m3,

    − available results of human and animal studies do not allow to determine the dose-effect relationship,

    − due to the genotoxic, carcinogenic, teratogenic and reproductive effects of etoposide, NIOSH established that the OEL should be set at a level below 0.01 mg/m3,

    − according to the classification proposed by the group operating within the framework of the “Global strategy of risk management”, etoposide should be in category 4, i.e., substances for which the OEL value in the work environment should be in the range of 0.001–0.01 mg/m3.

    The MAC value of etoposide was proposed at the level of the concentration equivalent to 0.1% of the lowest therapeu­tic dose used in humans (2.37 mg/kg), similar to other cytostatics (e.g., N-hydroxyurea, fluorouracil). An additional uncertainty factor “F” of 10 was adopted, related to the long-term effects of exposure, i.e., genotoxic, carcinogenic and reprotoxic effects of the substance. The MAC of the inhalable fraction of etoposide was set at 0.0017 mg/m3. There is no substantive basis to establish the value of the short-term (STEL) and permissible concentrations in biological material (DSB) for etoposide. Based on quantitative data characterizing skin absorption of etoposide, which has a molecular weight of 588.56 and its poor solubility in water, it has been found that the substance is characterized by a low ability to penetrate the skin. Due to the observed embryotoxicity in humans and teratogenic and embryotoxic etoposide in laboratory animals, the substance was marked with the letters “Ft” – a substance harmful for reproduction. In addition, the “Carc 1B” labeling recommended by the manufacturers, which indicates that this is a category-1B carcinogenic substance, has been accepted. This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



    Fluorouracil − inhalable fraction. Documentation of proposed values of occupational exposure limits (OELs)
    mgr inż. Małgorzata Kupczewska-Dobecka

    Fluorouracil is a cytostatic drug. Occupational exposure to fluorouracil occurs during its manufacture, packaging and use in hospital wards in a daily treatment practice. The maximum concentration of fluorouracil in workplace air of phar­macy technicians and nurses was 82.26 × 10-6 mg/m3. 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 in concentrations up to 75 μg/m3 during product weighing operations. The main effects of fluorouracil toxicity have been described in treated patients and they include bone marrow 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, a patient at the therapeutic dose of 2.5 mg/kg/day showed oral mucositis and glottis. Fluorouracil manufacturers indicate in safety data sheets the possibility of health effects in workers including sys­temic effects after prolonged exposure through the respiratory system and through the skin, manifested by bone marrow suppression and cardiotoxicity. 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 1987 IARC experts estimated that there was no evidence of carcinogenicity of fluorouracil in humans and animals, and ranked it in 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. In a study on Syrian hamsters, which were exposed to a fluorouracil aerosol 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. It was proposed to adopt the MAC value of fluorouracil at the concentration equivalent to 0.1% of the lowest therapeutic dose in the literature found in humans of 5 mg/kg. An uncertainty factor at level 10 associated with long-term effects of exposure, i.e., genotoxic and reprotoxic effects, was also adopted. A MAC value of fluorouracil has been proposed – inhalable fraction of 0.0035 mg/m3. There are no data to determine the short-term value. There are no grounds to establish the concentration limit value in biological material. According to the criteria adopted by the Expert Group for Chemical Agents , the term “skin” should be used – the absorption of substances through the skin may be as important as in the case of inhalation and “Ft” – substance harmful to reproduction. This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



    2-Nitroanisole. Documentation of occupational exposure limits (OELs)
    prof. dr hab. Andrzej Starek

    2-Nitroanisole is a colorless to yellowish liquid poorly soluble in water. It is used primarily to o-anisidine and o-dianisidine synthesis, which are precursors of azo dyes. 2-Nitroanisole has harmonized classification in the European Union: Carc. 1B 4 – carcinogenic, 1B category; H350 – may cause cancer after exposure trough the respiratory tract or skin; Acute Tox. 4 – acute toxicity 4; H302 – it acts adversely after swallowing. Occupational exposure to this compound oc­curs during its production and application. In Poland in 2016 203 workers were exposed to 2-nitroanisole. No data on 2-nitroanisole toxicity in humans were found in the available literature. In rodents 2-nitroanisole did not demonstrate large toxicity after administration in a single dose. In these animals repeatedly treated with this compound an increase in parenchymatous organ weights, decrease in body weight and also methemoglobinemia and hemolytic anemia were observed. 2-Nitroanisole was mutagenic in bacterial tests, induced gene mutations, chromosomal aberrations and sister chromatid exchange, and also damaged DNA (positive commet test). In rodents 2-nitroanisole induced both preneoplastic and neoplastic alterations mainly in urinary bladder, kidneys, and large intestine. The maximum admis­sible concentration (MAC) value for 2-nitroanisole has been calculated on the basis of the results of a short term exper­iment performed on rats. The critical effects observed were an increase in both liver and spleen weight and hemolytic anemia. On the basis of the NOEL value at the level of 8 mg/kg bw./day and uncertainty factors of 36, a MAC value at the level of 1.6 mg/m3 was obtained. On basis of literature data urinary bladder cancer risk associated with 1.6 mg/m3 concentration of 2-nitroanisole and a lifetime occupational exposure (40 years) was calculated at 2 × 10-3, which may be recognized as acceptable risk. The MAC has “Carc. 1B” notation (carcinogenic substance, 1B category).

    This article discusses the problems of occupational safety and health, which are covered by health sciences and envi­ronmental engineering.



    Zinc dichloride. Determination in workplace air
    mgr Jolanta Surgiewicz

    Zinc chloride is very soluble in water. It is used in galvanic processes, for wood impregnation, in the textile industry, in organic synthesis and for the production of explosives, for example smoke candles. Zinc dichloride has an irritating, corrosive and damaging effect on the eyes, mucous membranes of the airways, causes severe pneumonia, skin burns and systemic poisoning. Maximum allowable concentration value (MAC) for the inhalable fraction of zinc dichloride in Poland is 1 mg/m3 and the short-term exposure limit value (STEL) is 2 mg/m3. The aim of the study was to amend standard PN-Z-04367:2008 and to develop a method for determining zinc dichloride in workplace air in the range from 1/10 to 2 MAC values. The developed method of determination is based on taking a sample of air into two membrane filters, washing out zinc dichloride from the filters with deionized water and determining that compound as zinc by atomic absorption spectrometry (F-AAS) with atomization in air-acetylene flame. The method allows determination of zinc dichloride in the workplace air in the concentration range of 0.07–2.17 mg/m3 (for an air sample with a volume of 720 L, which corresponds to 0.1–2.2 of the MAC value. The method is characterized by good precision and accuracy and meets the requirements of European Standard PN-EN 482 for procedures for the determination of chemical substances. The method for the determination of zinc dichloride has been recorded in the form of an analytical procedure (see Appendix). This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



    3,3’-Dimethoxybenzidine. Determination in workplace air
    dr Joanna Kowalska, dr inż. Anna Jeżewska

    3,3’-Dimethoxybenzidine (DMOB) is a substance classified as a carcinogen. The recommended maximum admissible concentration (MAC) value for this substance in workplace air is 0.2 mg/m3. The aim of this study was to develop and validate a sensitive method for the determination of 3,3’-dimethoxybenzidine concentrations in workplace air in the range from 1/10 to 2 MAC values, in accordance with the requirements of standard PN-EN 482. The method consists in passing air that contains DMOB through a sulfuric acid-treated glass fiber filters, washing out the substance settled on the filter, using water and solution of sodium hydroxide, liquid-liquid extraction with toluene, replacing dissolvent with acetonitrile and analyzing the obtained solution. Studies were performed using high-performance liquid chromato­graphy (HPLC) technique. An Agilent Technologies (Germany) liquid chromatograph, series 1200, with a fluorescence detector (FLD) was used in the experiment. In the test, an Ultra C18 column of dimensions: 250 x 4.6 mm, with a 10 x 4.0 mm precolumn (Restek, USA) was applied. This method is linear within the 1.08 μg/ml to 21.60 μg/ml working range, which is equivalent to air concentrations from 0.02 to 0.4 mg/m3 for a 54-L air sample. The analytical method described in this paper allows for selective determination of 3,3’-dimethoxybenzidine in workplace air in the presence of 1,4-phe­nylenediamine, benzidine, aniline, 3,3’-dimethylbenzidine, 2-nitrotoluene, 3,3’-dichlorobenzidine and azobenzene. The method is characterized by good precision and accuracy and meets the criteria for the performance of procedures for the measurement of chemical agents, listed in EN 482. The method may be used for the assessment of occupational exposure to 3,3’-dimethoxybenzidine and the associated risk to workers’ health. The developed method of determining 3,3’-di­methoxybenzidine has been recorded as an analytical procedure (see appendix). This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



    Dimethyl phthalate. Determination in workplace air
    inż. Agnieszka Woźnica

    Dimethyl phthalate (DMP) is a colourless liquid with a slight aromatic odour. It is used in industry as a plasticizer of plastics and as an ingredient of fragrances in the production of cosmetics and detergents. Occupational exposure to DMP can occur through inhalation or ingestion. The aim of this study was to validate the method for de­termining DMP concentration in workplace air in the range from 1/10 to 2 MAC values, in accordance with the requirements of standard PN-EN 482. The study was performed using a gas chromatograph (GC) with a flame ionization detector (FID) equipped with a capillary column HP-INNOWAX (60 m × 0.25 mm, 0.15 μm). This method is based on the sorption of dimethyl phthalate vapours on a glass microfiber filter, desorption with ethanol, and analyzed by GC-FID. The average desorption efficiency of DMP from the filter was 98%. The application of an HP-INNOWAX column makes a selective determination of DMP in the presence of other solvents possible. The mea­surement range was 0.5 – 10 mg/m3 for a 120-L air sample. Limit of detection: 0.02 μg/ml and limit of quantification: 0.06 μg/ml. The analytical method described in this paper enables selective determination of DMP in workplace air in the presence of other solvents at concentrations from 0.5 mg/m3 (1/10 MAC value). The method is characterized by good precision and accuracy and meets the criteria for the performance of procedures for the measurement of chemical agents, listed in EN 482. The method may be used for the assessment of occupational exposure to DMP and the associated risk to workers’ health. The developed method of determining DMP has been recorded as an analytical procedure (see appendix). This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



    Calcium hydroxid. Determination in workplace air
    mgr Jolanta Surgiewicz

    Calcium hydroxide is a white color solid. It is used in construction, chemical industry, water purification and wastewater treatment, flue gas desulphurization. Calcium hydroxide causes serious damage to the eyes, irritates the skin and it can cause after-launch respiratory irritation. Maximum allowable concentration value (MAC) for calcium hydroxide in the work environment in Poland, for the inhalable and respirable fraction is 2 mg/m3 (STEL is 6 mg/m3) and 1 mg/m3 (STEL is 4 mg/m3), respectively. The aim of the study was to develop a method for determining the concentration of calcium hydroxide present in the inhalable and respirable fraction in the workplaces atmosphere, in the range from 1/10 to 2 MAC values in accordance with the requirements of European Standard PN-EN 482. The developed method is based on collecting, stopping calcium hydroxide (contained in the inhalable and the respirable fraction) on membrane filters, mineralizing filters with concentrated nitric acid and determining calcium of the resulted solution by atomic absorption spectrometry with atomization in acetylene-air flame (F-AAS). The described method allows the determination of calcium in workplace air concentrations in the range of 0.50–20.00 μg/ml. The calibration curve characterized by a high value of the correlation coefficient: R2 = 1.0000. The limit of detection (LOD) is 0.1 ng/ml and the limit of quantification (LOQ) is 0.3 ng/ml. The determined coefficient of recovery is 1.00. An analytical method allows the determination of the concentration of the calcium hydroxide present in the workplace air in the inhalable fraction in the concentration range of 0.10–4.11 mg/m3 (sample air volume 720 L) and in the reparable fraction in the concentration range 0.07–2.70 mg/m3 (for a sample air volume of 684 L), which represents 0.05–2.1 MAC value for the inhalable fraction and 0.07–2.7 MAC value for the respirable fraction. The method has good precision and accuracy and meets the requirements of European Standard PN-EN 482 for procedures for determining chemical agents. The method for determining calcium hydroxide has been recorded in the form of an analytical procedure (see Appendix). This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



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