PRINCIPLES AND METHODS OF ASSESSING THE WORKING ENVIRONMENT

NUMBER 2 (104) 2020




2-Naphthylamine and its salts – calculated as 2-naphthylamine Documentation of proposed values of occupational exposure limits (OELs)
EWELINA CZUBACKA, SŁAWOMIR CZERCZAK

2-Naphthylamine (2-NA) occurs in a form of colourless crystals with a weak, aromatic odour, which turn pink under the influence of light. The substance does not occur naturally in nature. The production of the 2-naphthylamine on an industrial scale is now banned in the UE. In the past this substance was used in the production of azo dyes, as an antioxidant in the rubber industry and in cable factories. 2-Naphthylamine is used in small amounts mainly in research laboratories. According to the data from the Polish Registry on Exposure to Chemicals, Their Mixtures, Factors or Technological Processes on Carcinogenic or Mutagenic Effects, 208 workers working in university laboratories, institutes, inspections, control offices as well as in laboratories of pharmaceutical and paint production plant were exposed to 2-NA and its salts in Poland in 2017. According to Annex XVII of REACH Regulation, 2-naphthylamine and its salts shall not be placed on the market, or used, as substances or in mixtures in concentrations greater than 0,1 % by weight. In occupational exposure to 2-naphthylamine and its salts, respiratory tract and skin are more important than gastrointestinal absorption.

Most of the absorbed dose of 2-naphthylamine is mainly excreted in the urine. Median doses or lethal concentrations of 2-naphthylamine that were obtained in experimental animal studies indicate that it is harmful if swallowed.

The main symptoms of acute intoxication are conjunctival redness, watery eyes, blue mucosa, nails, skin, pain and dizziness, shortness of breath. Based on the results of studies available in the literature, the effects of 2-naphthylamine under subchronic and chronic exposure may include contact dermatitis, chronic cystitis and bladder cancers. 2-Naphthylamine and its salts are compounds with proven carcinogenic humans. In 1974, The International

Agency for Research on Cancer recognized 2-naphthylamine as a human carcinogen (group 1) based on sufficient evidence of a carcinogenic effect on humans. According to the CLP Regulation, 2-naphthylamine and its salts are classified as carcinogenic category 1A substances with the assigned hazard code H350 (May cause cancer) and as acute toxicity category 4 with the hazard code H302 assigned (Harmful if swallowed). In Poland, MAC (Maximum Admissible Concentration) value for 2-naphthylamine was set at 0 mg/m3. In other EU countries, only France has set a MAC value of 0.005 mg/m3 while Hungary and Italy have a short-term value of 0.005 mg/m3 and 0.001 mg/m3, respectively. Taking the Slope Factor for humans published by the California EPA and taking into account the accepted risk value of 10-4 for the occurrence of additional cases for bladder cancer, the MAC value for 2-naphthylamine and its salts is proposed to be 0.003 mg/m3. The letters “Carc. 1A” should be used – the substance has carcinogenic potential for humans. This article discussess the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



4-Aminotoluene (p-toluidine) Documentation of proposed values of occupational exposure limits (OELs)
RENATA SOĆKO, JAN GROMIEC

4-Aminotoluene (p-toluidine) has the form of white, lustrous plates or leaflets with a characteristic wine-like odour. The substance is manufactured and / or imported into the European Economic Area in the amount of 1000–10.000 t / year. Five registrants from Germany registered the substance on ECHA’s website. 4- Aminotoluene is used as an intermediates in the manufacture of many dyes, resins, pesticides, pharmaceuticals and in the synthesis of organic chemicals. About 1000 t of 4-aminotoluene / year is used for the production of pesticides, including an insecticide called Fipronil and a fungicide Tolylfluanid. The substance is also used in laboratories as a reagent for lignin, nitrile and phloroglucinol. 4- Aminotoluene is included in draft Directive (Chemical Agents Directive 98/24 / EC) establishing the 5th list of indicative occupational exposure limit values with values: OEL: 4.46 mg / m3; STEL: 8.92 mg / m3, much lower than the obligatory MAC value at 8 mg/m3 in Poland therefore the monograph with the hygienic standard proposal has been developed again. As far as occupational exposure to 4-aminotoluene (production and use) is concerned, the route of exposure is significant: inhalation and dermal contact. Taking into consideration health effects, 4-aminotoluene is classified as toxic by inhalation, in contact with the skin and if swallowed, irritating to eyes, sensitising by skin contact and carcinogenic cat. 2 (suspected of causing cancer). A review of scientific literature showed that exposure to 4-aminotoluene affects blood (methemoglobin inducer) and the liver. The basis for calculating the proposed MAC value was the methaemoglobinogenic effect of 4-aminotoluene recorded in a 1- and 3-month study on Wistar rats, which were given 4-aminotoluene with feed containing 4% or 14% fat, in doses: 0; 40; 80 or 160 mg/kg/day. 4-Aminotoluene caused statistically significant, dose-related increases in the level of methaemoglobin in the blood compared to control animals. Based on the above  effect, the 40 mg / kg / day dose was taken as the LOAEL value and the OEL value was calculated from it. It was proposed to adopt an OEL value of 4-aminotoluene at 4.4 mg /m3, i.e. as it is in the draft directive establishing the 5th list of indicative

occupational exposure limit values according to Directive 98/24 / EC. The instantaneous value of OELs was proposed at the level of 8.8 mg/m3. This value should protect employees against possible eye irritation. Due to the eye irritation of 4-aminotoluene, it was proposed to label the compound with the letter “I” (irritant), and because of the LD50 after administration to the skin of a rabbit of 890 mg/kg. – information on skin absorption (‘skin’ – absorption of the substance through the skin may be just as important as when inhaled). 4-Aminotoluene according to the harmonized classification was classified as a skin sensitiser, therefore it was proposed to introduce the notation with the letter “A” – a substance with sensitizing effect. Skin sensitization has been demonstrated in guinea pigs and in people allergic to p-phenylenediamine, in which a cross reaction to 2% 4-aminotoluene has been reported. It was proposed to leave the limit value as admissible concentration in biological material (DSB) at the level recommended for methaemoglobinogenic substances, i.e. 2% of methaemoglobin in the blood. This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



5-Fluorouracil – inhable fraction. Determination method in workplace air
Marzena Bonczarowska, Sławomir Brzeźnicki

5-Fluorouracil (5-FU) at room temperature is a fine white crystalline odorless powder. 5-FU is one of the most widely used cytotoxic drug and has a strong antitumor activity in gastrointestinal tract cancer, especially of colorectal cancer. Occupational exposure to 5-fluorouracile (mainly via skin contact or via inhalation route) may occur among group of healthcare workers or workers employed in the production of this drug. Exposure to 5-FU can cause suppression of bone marrow function, cardiotoxicity and in the case of skin contact, skin irritation or allergic skin reactions. The aim of this study was to develop and validate a sensitive method for determining the concentration of 5-fluorouracil 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 liquid chromatograph with spectrophotometric detection (HPLC-UV-VIS). All chromatographic analysis were performed with XTerra C-18 150 . 2.1 mm . 3.5 mm analytical column, which was eluted with mixture of acetonitrile and water with 0.1% of formic acid. This method is based on the collection of 5-FU on glass fiber filter, extraction with mixture of acetonitrile:water with addition of formic acid (0.1%), and chromatographic determination of resulted solution with HPLC-UV-VIS. The average recovery factor of 5-FU from filters was 0.93. The method is linear (r = 0.999) within the investigated working range of 0.052–2,6 μg/ml. The calculated limit of detection (LOD) and limit of quantification (LOQ) were 0.007 and 0.022 μg/ml, respectively. The analytical method described in this paper, thanks to the UV-VIS detection technique and Xterra analytical column, makes it possible to selectively determine 5-FU in workplace air in the presence of other compounds at concentrations from 0.00014 mg/m3 (1/25 MAC value). The method is precise, accurate and it meets the criteria for procedures for measuring chemical agents listed in standard EN 482. This method can be used for assessing occupational exposure to 5-FU and associated risk to workers’ health. The developed method of determining 5-FU has been recorded as an analytical procedure (see appendix). This article discussess the problems of occupational safety and health, which are covered by health sciences and environmental engineering.



Cyclohexyl isocyanate Determination in workplace air with high-performance liquid Chromatography
SŁAWOMIR BRZEŹNICKI, MARZENA BONCZAROWSKA

Cyclohexyl isocyanate (ICH) is produced in dehydratation reaction of N-cyclophosphorylamide. ICH is a colorless to pale yellow liquid with a sharp acrid odor. ICH is mainly used in manufacturing cyclohexyl carbamates or ureas for agricultural chemicals or pharmaceutical use. It is also used in polyurethane plastics, rubber or other plastics. Adverse effect of ICH is related to its irritant and sensitizing properties. As other isocyanates, it is irritating to the skin, mucous membranes, eyes and respiratory tract. Occupational exposure to ICH vapors can cause asthma. The aim of this study was to develop and validate a sensitive method for determining ICH 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 study was performed using a liquid chromatograph equipped with spectrofluorometric detector (FLD). All chromatographic analysis were performed with Ascentis Express RP-Amide 250 × 3 mm analytical column, which was eluted with acetonitrile and water mixture. This method is based on the collection of ICH on glass fiber filter coated with 1-(2-pyridyl)piperazine solution, extraction of formed derivatives with mixture of acetonitrile with dimethylsulfoxide and chromatographic determination of resulted solution with HPLC technique. The average recovery of ICH from filters was 0.93. This method is linear (r = 0.9991) within the investigated working range of 0.27–5.33 μg/ml, which is equivalent to air concentrations from 0.004–0.08 mg/m3 for a 200-L air sample. Calculated limit of detection (LOD) and limit

of quantification (LOQ) of ICH were 0.0056 and 0.019 μg/ml respectively. The method described in this paper makes it possible to selectively determine ICH in workplace air in the presence of other compounds at concentrations of 0.004 mg/m3 (< 1/10 MAC value). This method is precise, accurate and it meets the criteria for procedures for measuring chemical agents listed in standard PN EN 482. This method can be used for assessing occupational exposure to ICH and associated risk to workers’ health. The developed method of determining ICH 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.



3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate Determination in workplace air with high-performance liquid chromatography
Sławomir Brzeźnicki, Marzena Bonczarowska

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate (isophorone diisocyanate, DIF) is a colorless to pale yellow liquid. It is commonly used in the manufacturing of polyurethane of high chemical and mechanical resistance. It is also used in the production of paints, lacquers, fabric coatings and so called lightweight gypsum. Occupational exposure to DIF can cause severe irritant effects on mucous membranes, the respiratory tract and the eyes, and an acute attacks of an asthma. The aim of this study was to develop and validate a sensitive method for the determination of DIF 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 study was performed using a liquid chromatograph equipped with a spectrofluorimetric detector (FLD). All chromatographic analyses were carried out using an Ascentis Express RP-Amide 250 x 3 mm analytical column. The described method is based on the collection of DIF on a glass fiber filter impregnated with 1-(2-pyridyl)piperazine solution, extraction of formed derivative with mixture of acetonitrile: dimethylsulfoxide and chromatographic analysis of resulted solution by means of HPLC technique. The average recovery of DIF from filters amounted to 0.94. The method is linear (r = 0.9992) within the investigated working range 0.027–5.33 μg/ml, which is equivalent to air concentrations from 0.004–0.08 mg/m3 for a 200-L air sample. The calculated limit of detection (LOD) and limit of quantification (LOQ) of DIF amounted to 0.00032 and 0.0017 μg/ml respectively. The described method enables selective determination of DIF in workplace atmosphere in the presence of other compounds at concentrations from 0.004 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 and the associated risk to workers’ health. The method for determining DIF 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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