PRINCIPLES AND METHODS OF ASSESSING THE WORKING ENVIRONMENT

NUMBER 1 (91) 2017




  • Hydrogen cynide and cyanide salts: sodium, potassium, calcium, as CN-.  Documentation of proposed values of occupational exposure limits (OELs)
    Jolanta Skowroń, Katarzyna Konieczko , p. 5
  • Cumene. Documentation of proposed values of occupational  exposure limits (OELs)
    Agnieszka Jankowska, Słowimir Czerczak, p. 65
  • Nitroethane. Documentation of proposed values  of occupational exposure limits (OELs)
    Andrzej Sapota, Anna Kilanowicz, Małgorzata Skrzypińska-Gawrysiak , p. 98
  • Maleic anhydride. Determination in workplace air
    Agnieszka Woźnica , p. 116
  • Diethyl phthalate. Determination in workplace air  
    Agnieszka Woźnica , p. 128
  • Adipic acid. Determination in workplace air  
    Elżbieta Dobrzyńska  , p. 140
  • n-Butyl acetate and its isomers – isobutyl acetate and sec-butyl acetate. Determination in workplace air
    Joanna Kowalska , p. 152
  • Hydrogen cynide and cyanide salts: sodium, potassium, calcium, as CN-.  Documentation of proposed values of occupational exposure limits (OELs)
    Jolanta Skowroń, Katarzyna Konieczko

    Hydrogen cyanide (HCN) and its salts: potassi-um cyanide (KCN), sodium cyanide (NaCN) and calcium cyanide [Ca(CN2)] are very toxic. Hydrogen cyanide at ambient conditions is a colourless liquid or a colourless gas with the characteristic odour of bitter almonds. Sodium, potassium and calcium cyanides are white hygroscopic, crystalline solids with a slight HCN odour.
    Hydrogen cyanide is used mainly in a fumigation of ships, buildings, orchards and various foods, in electroplating, in the production of chelating agents such as EDTA, and in metal treament processes. It is also used as a chemical in-termediate.
    Cyanides are used in the extraction and recovery of gold and silver from ores, the heat treatment of metals, and electroplating. They are also precursors in chemical syntheses.
    Workers from metal, electrochemical, plastics, pharmaceutical, textile, chemical and food industries are exposed to these compounds.
    In 2008–2013, there were no workers exposed to the concentration of hydrogen cyanide and sodium, potassium and calcium cyanides exceeding the maximum admissible ceiling concentration MAC(C) 5 mg/m3 (the national database maintained by the Regional Sanitary Station in Bydgoszcz).
    Hydrogen cyanide and cyanides are irritating to mucous membranes and skin. They are absorbed by inhalation, dermal and oral exposure.
    The acute hydrogen cyanide and cyanides poisoning indicate a great danger and hazard, because these compounds are quickly absorbed into the body and their effects are present within a few minutes after the start of exposure.
    Exposure to sodium cyanide at a concentration of 286 mg/m3 or to hydrogen cyanide at a concentration greater than 300 mg/m3 for 1 min may be fatal. Sodium, potassium or calcium cyanides at concentrations of 25 mg/m3 are direct hazards to life and health of workers if exposure lasts about 30 min and without respiratory protection. For hydrogen cyanide this value was established as
    56 mg/m3. The development of symptoms of acute poisoning by hydrogen cyanide or cyanides in humans occurs in three phases: breathlessness and excitement, convulsions and paralysis.
    The results of studies of subchronic and chronic exposures of workers to cyanides by inhalation indicate that symptoms of exposure were associated with changes in the central nervous system (headache, weakness, changes in the sensation of taste and smell) and damage to the thyroid (enlargement, changes in uptake of iodine, elevated concentration of thyroid stimulating hormone TSH and a reduction of thyroid hormones T3 and T4). Other studies suggest that chronic exposure to hydrogen cyanide in the hardening plant of metals caused decrements in lung functions among workers.
    Hydrogen cyanide and cyanides, both in aqueous solution, applied to the conjunctival sac or on the skin is quickly absorbed into the body of animals in amounts sufficient to cause toxic effects and death.
    In rats and mice treated with sodium cyanide in drinking water at a dose of 4.5 mg/kg bw/day for 13 weeks, no significant changes in biochemical and haematological parameters of peripheral blood and histopathological findings in the internal organs were observed. There were no pathological changes in the respiratory, cardiovascular, nervous system and kidneys in rats which were feed with hydrogen cyanide over two years. Calculated NOAEL was approximately 10.4 mg/kg body weight.
    There is no available data on the carcinogenicity of hydrogen cyanide and cyanides in human and animals.
    Positive effects were obtained in one study only, in which hydrogen cyanide was tested with Salmonella typhimurium strain TA 100 in the absence of metabolic activation, while the other strains employed in this study yielded negative results. Cyanides did not show mutagenic activity in the tests in vitro and in vivo.
    On the basis of the studies on hamsters, teratogenic effects of sodium cyanide were observed. This compound was toxic for pregnant mothers and caused an increase in fatal resorption and malformations in an offspring.
    The results of the study of workers exposed to hydrogen cyanide and cyanides and with changes in thyroid were the basis for calculating MAC (NDS) value. The LOAEL value was establishes as a concentration of  4.7 mg/m3.
    The MAC of 1 mg/m3 (calculated CN–) was established for hydrogen cyanide and the inhalable fraction of sodium, potassium, calcium cyanides was accepted.
    Due to totally different mechanism of action of hydrogen cyanide and cyanides (sodium, potassium, calcium) in chronic exposure (effects on the thyroid gland) and in the acute exposure, which is primarily associated with inhibition enzymatic system of cytochrome c oxidase, which prevents cells from using oxygen (histotoxic hypoxia), for these compounds the ceiling value MAC(C) of
    5 mg/m3 was not changed.
    Such an approach is a deviation from the basic methodology adopted by the Group of Expert and the Interdepartmental Commission for MAC and MAI. MAC and ceiling MAC(C) values for these substances should be establish due to the different effects of critical action and mechanisms of action in the acute and chronic condition.
    This approach is consistent with the DECOS Committee (Dutch Expert Committee on Occupational Standards) from 2002. According to the committee, the acute human data show the most sensitive effect, i.e., death. The steepness of the doseresponse relationship and the severity of the acute effects in humans imply at the same time that utmost care should be taken to prevent this exposure level from being exceeded, not even for
    a short time. Therefore, the committee proposed to establish a ceiling value for the acute health effects of 10 mg/m3 for hydrogen cyanide.
    The Scientific Committee on Occupational Exposure Limit Values (SCOEL) proposed an OEL value of 1 mg/m3. However, since the acute effects in humans are severe (i.e., death) and show a rather steep doseresponse relationship, peak exposures should be avoided. Based on the steepness of the doseresponse relationship and the severity of the acute effects in humans a STEL of 5 mg/m3 is recommended as CN– from any combination of the three compounds.
    Based on the very high skin permeability measured for hydrogen cyanide and cyanide anions in aqueous solutions, a skin notation is recommended for hydrogen cyanide and sodium, potassium, calcium cyanides.



    Cumene. Documentation of proposed values of occupational  exposure limits (OELs)
    Agnieszka Jankowska, Słowimir Czerczak

    Cumene is a clear, colourless liquid with a strong aromatic gasoline-like odour. Cumene is used for the synthesis of phenol and acetone and as a solvent in paints, varnishes and resins. It is also used in the printing and rubber industries.
    According to data from Polish Chief Sanitary Inspectorate, in 2010, no workers were occupa-tionally exposed to cumene in concentrations exceeding Polish OEL values (100 mg/m3). In 2014, 51 workers were exposed to cumene in concentrations from 0.1 to 0.5 MAC value (from 10 mg/m3 to 50 mg/m3).
    Cumene vapours are irritating to the respirato-ry tract. In humans, high concentrations of cu-mene cause painful irritation to the eyes and the respiratory tract. In animals, cumene causes mainly CNS depression. Chronic exposure to cumene can cause hepatotoxicity.
    In vitro tests indicated no mutagenic and no genotoxic potential of cumene. Intraperitoneal injection of cumene induced micronuclei in bone marrow of rats. Dose-related increases in DNA damage were observed in liver cells of male rat and lung cells of female mouse. A me-tabolite of cumene, α-methylstyrene, was not mutagenic in bacterial tests but induced chromo-somal damage in cell cultures and rodent cells.
    IARC experts classified cumene in group 2.B – chemicals possibly carcinogenic to humans based on sufficient evidence in experimental animals for the carcinogenicity of cumene. Ex-posure of mice to cumene by inhalation in-creased the incidence of alveolar/bronchiolar adenoma and carcinoma in males and females mice, haemangiosarcoma of the spleen in male mice and hepatocellular adenoma in female mice. Exposure of rats to cumene by inhalation increased the incidence of nasal adenoma in males and females and renal tubule adenoma and carcinoma in male rats.
    Cumene is well absorbed. It is a lipophilic substance which is well distributed in the whole body. Cytochrome P-450 is involved in cumene me-tabolism. Main metabolite identified in urine was 2-phenyl-2-propanol and in exhaled air α-methylstyrene.
    In 2014, Scientific Committee for Occupational Exposure Limits to Chemical Agents (SCOEL) prepared change of indicative OEL for cumene – reduction of concentration from 100 mg/m3 (directive 2000/39/WE) to 50 mg/m³, STEL value 250 mg/m3 remain unchanged. The com-pound was included in SCOEL carcinogenicity group D (not genotoxic and not affecting DNA chemicals), for which a health-based OEL may be derived on the basis of NOAEL value. Po-land did not submit any comments on SCOEL proposal during public consultations in 2014. A new indicative OEL was derived on the basis of 3-month NTP inhalation studies in rats and mice. SCOEL established 310 mg/m³ (62.5 ppm) level as a NOAEC for hepatotoxici-ty. A STEL of 250 mg/m3 (50 ppm) have been recommended to protect against respiratory tract irritation and behavioural effects. Moreover, a “skin notation” was recommended because of its probable skin penetration. BLV recommended by SCOEL is 7 mg 2-phenyl-2-propanol per gramme of creatinine in urine (after hydrolysis).
    To determine MAC value for cumene hepato-toxicity and nephrotoxicity were adopted as a critical effect. The Expert Group for Chemi-cals Agents established 310 mg/m³ as NO-AEC based on 3-month NTP inhalation stud-ies in rats and proposed reduction of the cur-rent MAC value from 100 to 50 mg/m3. It was agreed that the previous STEL value of 250 mg/m3 should remain unchanged, which is also in accordance with the value recom-mended by SCOEL. Recommended BEI value is 7 mg 2-phenyl-2-propanol per gramme of creatinine in urine (after hydrolysis), sampled immediately after work shift. It was recom-mended to remain “I” (irritant) and “Sk” (substance can penetrate skin) labelling of cumene.



    Nitroethane. Documentation of proposed values  of occupational exposure limits (OELs)
    Andrzej Sapota, Anna Kilanowicz, Małgorzata Skrzypińska-Gawrysiak

    Nitroethane is a colorless oily liquid with a mild fruity odor. It is used mainly as a propel-lant (e.g., fuel for rockets), and as a solvent or dissolvent agent for cellulose esters, resins (vinyl and alkyd) and waxes, and also in chemical syn-thesis.
    Occupational exposure to nitroethane may occur during the process of its production and pro-cessing. There are no data on air concentrations of nitroethane in occupational exposure. In 2010–2015, workers in Poland were not exposed to nitroethane concentrations exceeding the maximum allowable value – 75 mg/m3 (the limit value valid since 2010).
    Nitroethane can be absorbed into the body via inhalation of its vapors or by ingestion.
    The discussed cases of nitroethane acute poison-ing caused by an accidental ingestion of artificial fingernail remover containing pure nitroethane concerned children under three years. Few hours after ingestion, cyanosis and sporadic vomiting were observed in children. The methe-moglobin level reached 40÷50%.
    Neither data on chronic nitroethane poisoning in humans nor data obtained from epidemiological studies are available.
    On the basis of the results of acute toxicity stud-ies nitroethane has been categorized in the group of hazardous compounds. However, eye and dermal irritation or allergic effects have not been evidenced.
    The studies of sub-chronic (4 and 90 days) and chronic (2 years) exposure to nitroethane per-formed on rats and mice (concentration range 310 ÷ 12 400 mg/m3) revealed the methemoglo-binogenic effect of this compound and a minor damage to liver, spleen, salivary gland and nasal turbinates.
    Niroethane has shown neither mutagenic nor carcinogenic effects. Its influence on fertility has not been evidenced either.
    After chronic exposure (2 years) of rats to ni-troethane at concentration of 525 mg/m3 (the lowest observed adverse effect level – LOAEL), a slight change in a body mass of exposed female animals and subtle changes in biochemical pa-rameters were observed, but there were no anomalies in hematological and histopathologi-cal examinations.
    The value of 62 mg/m3 has been suggested to be adopted as the MAC value for nitroethane after applying the LOAEL value of 525 mg/m3 and relevant coefficients of uncertainty. The STEL value for nitroethane was proposed according to the methodology for determining short term ex-posure level value for irritating substances as three times MAC value (186 mg/m3) to prevent the effects of sensory irritations in humans. Be-cause of its methemoglobinogenic effect, 2% Met-Hb has been suggested to be adopted as the value of biological exposure index (BEI), like the value already adopted for all methemoglobino-genic substances.
    The Scientific Committee on Occupational Expo-sure Limits (SCOEL) proposed the time-weighted average (TWA) for nitroethane (8 h) as 62 mg/m3 (20 ppm), short-term exposure limit (STEL, 15 min) as 312 mg/m3 (100 ppm) and “skin” notation.
    Proposed OEL and STEL values for nitroethane were subjected to public consultation, conducted in 2011 by contact points, during which Poland did not raise any objections to the proposals. The proposed values for nitroethane by SCOEL has been adopted by the Advisory Committee on Safety and Health at Work UE (ACSH) and included in the draft directive establishing the IV list of indicative occupational exposure limit values.



    Maleic anhydride. Determination in workplace air
    Agnieszka Woźnica

    Maleic anhydride is a crystalline solid. Maleic anhydride is an important intermediate in the chemical industry.
    It is harmful, irritating and sensitizing.
    The aim of this study was to develop a new method for determining concentrations of maleic anhydride
    in workplace air in the range from 1/10 to 2 MAC values, in accordance with the requirements
    of Standard No. EN 482.
    The study was performed using a liquid chromatograph ( Agilent Technologies series 1200) with a diode
    array detector (DAD). The determination was performed in the reverse-phase system (mobile
    phase: acetonitrile: solution of phosphoric acid) using an Ultra C18 column (250 × 4.6 mm with dp =
    5 μm) with precolumn (10 × 4 mm). The method was based on passing air through a glass fiber filter
    coated with 3,4-di-methoxybenzylamine and di-noctyl phthalate. Samples were extracted with aqueous
    ammonium hydroxide and analyzed with HPLC. The method was validated according to
    Standard No. EN 482. The measuring range was 0.05  1 mg/m3, the limit of detection (LOD) was
    8.18 ng/ml, the limit of quantification (LOQ) was 24.5 ng/ml, the overall accuracy of the method was
    5.53% and the relative total uncertainty of the method was 12.02%.
    The analytical method described in this paper enables selective determination of maleic anhydride in
    workplace air in the presence of other substances at concentrations from 0.05 mg/m³ (1/10 MAC
    value). The method is precise, accurate and it meets the criteria for measuring chemical agents listed in
    Standard No. EN 482.
    The developed method of determining maleic anhydride has been recorded as an analytical procedure
    (see appendix).



    Diethyl phthalate. Determination in workplace air  
    Agnieszka Woźnica

    Diethyl phthalate (DEP) is an ester of phthalic acid and an ethanol. It is a colorless, oily liq-uid. This substance is used in industry as a solvent for cellulose acetate and nitrocellulose, and a plasticizer of plastics. It is added to nail polish, perfumes in cosmetics and detergents, food packaging and pharmaceuticals. Diethyl phthalate is a substance which is toxic if in-haled, irritating to eyes and skin, toxic for re-production (it is suspected that acts harmful to fertility or unborn child).
    The aim of this study was to develop and vali-date a method for determining concentrations of diethyl phthalate in workplace air in the range from 1/10 to 2 MAC values in accord-ance with the requirements of Standard No. PN-EN 482.
    The study was performed using a gas chro-matograph (GC) with a flame ionization de-tector (FID) with a capillary column HP-INNOWAX (60 m × 0.25 mm, 0.15 µm).
    The method is based on the adsorption of di-ethyl phthalate on glass microfiber filter, de-sorption of analysed compound with ethanol and analysis of  the  resulting  solution  with  GC-FID.  The
    average desorption efficiency of diethyl phthalate from filter was 90%. Application of column HP-INNOWAX enables selective de-termination of diethyl phthalate in the pres-ence of other solvents. The measurement range was 0.3  6 mg/m3 for a 240-L air sample. The limit of detection (LOD) and the limit of quan-tification (LOQ) are 0.09 µg/ml and 0.27 µg/ml, respectively.
    The analytical method described in this paper enables selective determination of inhalable fraction of diethyl phthalate in workplace air in the presence of other substances at concen-trations from 0.3 mg/m3 (1/10 MAC value). The method is precise, accurate and it meets the criteria for procedures for measuring chemical agents listed in Standard No. EN 482. The method can be used for assessing occupa-tional exposure to diethyl phthalate and asso-ciated risk to workers’ health.
    The developed method of determining diethyl phthalate has been recorded as an analytical procedure (see appendix).



    Adipic acid. Determination in workplace air  
    Elżbieta Dobrzyńska  

    Adipic acid is a colorless or white solid. On an industrial scale it is obtained by oxidation of cyclohexanol, cyclohexanone or their mixtures with nitric acid. The compound is utilized in the chemical industry in the production of polyure-thanes, polyamides and in the food industry, e.g., as an acidity regulator (E355). Adipic acid is irri-tating to the eyes.
    The aim of this study was to develop a method for determining inhalable fraction of adipic acid which enables determination of its concentrations in workplaces air in the range from 1/10 to 2 of MAC values.
    The developed method is based on the adsorp-tion of adipic acid on a glass fiber filter, a water-extraction and a gas chromatographic analysis of the
    resulting solution. The tests were performed using a liquid chromatograph (HPLC) 1200 series of
    Agilent Technologies with diode array detector (DAD). Determinations were performed with
    application of Allure Organic Acids column (15 cm x 4.6 mm, dp 5 µm). Validation of the method was conducted in accordance with the require-ments of the Standard No. EN 482. On the basis of the obtained results, the concentration range was established as 0.036 – 0.72 mg/ml, which corre-sponds to the concentration range of 0.5 – 10 mg/m3 for
    720-L air sample. In the following range the ob-tained calibration curve was linear as evidenced by the regression coefficient at the level of 0.9999. The overall accuracy of the method was 5.47% and its relative total uncertainty 23.88%.
    This method enables selective analytical deter-mination of adipic acid in workplace air at the concentration range 0.5 – 10 mg/m3 in the pres-ence of co-occurring compounds, such as cyclo-hexanone and isopropanol. The method for de-termining adipic acid is described in the form of analytical procedure in the annex.



    n-Butyl acetate and its isomers – isobutyl acetate and sec-butyl acetate. Determination in workplace air
    Joanna Kowalska

    n-Butyl acetate and its isomers, isobutyl acetate and sec-butyl acetate, are colorless, flammable liquids with a fruity odour. Because of their physicochemical properties they are commonly used as organic solvents and compounds of sol-vent mixtures in various industries.
    The aim of this study was to develop and vali-date a method for determining concentrations of n-butyl acetate, isobutyl acetate and sec-butyl acetate in workplace air.
    The determination method is based on the ad-sorption of n-butyl acetate and its isomers on activated charcoal (100/50 mg sections), desorp-tion with carbon disulfide and the analysis of the resulting solution with gas chromatography with flame ionization detection (GC-FID). A capillary column with HP-FFAP (50 m × 0.32 mm, i.d. × 0.50 μm film thickness) was used.
    The method is linear within the working range from 0.24 mg/ml to 4.8 mg/ml, which is equiva-lent to air concentrations from 24 to 480 mg/m3 for
    a 10-L air sample.
    The analytical method described in this paper enables selective determination of analytes in workplace air in presence of coexisting substanc-es. The method is precise, accurate and it meets the criteria for procedures for measuring chemi-cal agents listed in Standard No. EN 482. The method can be used for assessing occupational exposure to n-butyl acetate, isobutyl acetate and sec-butyl acetate and associated risk to workers’ health.
    The developed method of determining n-butyl acetate and its isomers (isobutyl acetate, sec-butyl acetate) has been recorded as an analytical pro-cedure (see appendix).



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