This article discusses the transposition process of Directive 2017/164/EU of January 31, 2017, establishing the fourth list of indicative occupational exposure limit values into national law, and the Directive 2017/2398/UE of December 12, 2017 amending Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work.

Nanotechnology is a rapidly evolving field allowing to design and obtain new, previously unknown nanostructured materials with unique properties and broad application. In addition to the wide range of potential benefits, the use of nanoobjects can also endanger human health. Due to the divergent results of published studies about impact of nanoobjects on health, different exposure measurement strategies and non-uniform and limited documentation the possibilities for comparing different measurements, and as well the use of research results to simulate and construct mathematical models are limited. In order to harmonize documentation, research results, exposure indicators and context for exposure measurement, the NECID (Nano Exposure and Contextual Information Database) database, a digital documentation platform for occupational exposure to nanoparticles, has been developed.

Potassium bromate (V), (KBrO3) exists as white crystals, crystalline powder or granules. It is highly soluble in water, tasteless and odourless.

Potassium bromate is a strong oxidizing agent. In the past it has been used as food additive in flour milling, as an ingredient in fish-paste in Japan, in cheese making, in beer malting, as a component of cold hair wave liquid and an oxidizing compound.

Moreover, bromate is formed as a by-product of water disinfection by ozonation and is frequently detected in tap and bottled water. In fact bromate is one of the most prevalent disinfection by-product of surface water.

Occupational exposure to potassium bromate occurs mainly in production plants during packaging processes. In Poland, about 1 160 persons were exposed to this compound in 2016.

Bromate caused many acute poisonings by accidental ingestion, mainly among children, and more often ingested for tentative suicide by young women, especially hairdressers.

In the acute phase of poisoning, gastrointestinal disturbances, irreversible hearing loss, and acute renal failure were observed. Acute renal failure was associated with hemolytic uremic syndrome. There are no data on chronic intoxication of humans by potassium bromate and epidemiological studies on this subject.

On the basis of the value of median lethal dose (LD50) per os in rat, potassium bromate has been classified as a compound belonging to the category „Toxic”.

Major toxic signs and symptoms in animals after a single intragastric administration of potassium bromate were tachypnea, hypothermia, diarrhea, lacrimation, suppression of locomotor movement, ataxic gait, and animals lying in a prone position.

At autopsy the major findings were strong hyperemia of glandular stomach mucosa and congestion of lungs. Microscopically, necrosis and degenerative changes of the proximal tubular epithelium and hearing cells of internal ear were found.

It was stated that the compound is not irritating, corrosive or sensitizing.

In subchronic and chronic exposure of rodents, potassium bromate led to liver and kidney dysfunction and tubular epithelial damage.

Potassium bromate had mutagenic and clastogenic effects. It induced point mutations, structural chromosome aberrations, micronuclei in polychromatic erythrocytes in male mice, DNA oxidative damage by modification of deoxyguanosine to 8-hydroxydeoxyguanosine, and DNA double-strand breakage.

Potassium bromate induced neoplasms in rodents and exerted promotion effect in comparison with well-known carcinogens. Besides from preneoplastic changes, expressed by high incidences of renal cell tumors and dysplastic foci, bromate induced solid neoplasms, such as adenomas and adenocarcinomas in a rat kidney and thyroid, and mesotheliomas of peritoneum and tunica vaginalis testis.

The European Union classified potassium bromate as a substance that can cause cancer (Group 1.B), whereas IARC classified it as a presumably carcinogenic agent for human (Group 2.B).

In principle, effects of bromate on reproduction and ontogenetic development of offspring were not observed.

Animal studies suggest that a kidney is a critical organ in the exposure to potassium bromate. The results of subchronic exposure of male rats to potassium bromate administered with drinking water were used to calculate the value of MAC-NDS. The critical effects in kidney were: an increase of organ weight and dose-dependent histopathological alterations defined as epithelium urinary tract hypertrophy. The NOAEL value is 1.5 mg/kg b.w./day. For the calculation of the maximum allowable concentration (MAC) value, 5 uncertainty factors with total value of 24 were used. Based on this estimation it is proposed to accept the MAC-TWA value for potassium bromate at 0.44 mg/m³.

The risks of kidney and thyroid cancer in condition of occupational exposure are 2.2 · 10^-3 and 0.6 · 10^-3, respectively.

There is no reason to determine the value of short-term exposure limit (STEL) and the biological exposure index (BEI). „Carc.1.B” notation (carcinogenic substance) was proposed.

3,3'-Dimethylbenzidine (3,3'-DMB, DMB, o-tolidine) is a solid used (as water-soluble dihydrochloride salt (dimethylbenzidine · 2HCl)) in the production of azopigments, polyurethane elastomers and plastics for coating. Small amounts are also used in diagnostic tests in laboratories.

Occupational exposure to dimethylbenzydine occurs mainly during the production and use of pigments to dye textiles, plastics, paper and leather. In 2005–2014, dimethylbenzidine was used in Poland in 18–30 workplaces, where 135–280 people each year (mainly women) were exposed. No epidemiological data and information related to toxic effects of DMB in humans was found in the available literature.

The LD50 value (median lethal dose) after single intragastric administration of 3,3'-dimethylbenzidine to rats was 404 mg/kg. After repeated exposure of laboratory animals, liver, kidney, thyroid injury and hematological changes were noted.

In the Ames tests with metabolic activation, it was found that metabolites of 3,3'-dimethylbenzidine show stronger mutagenic action than the parent compound. 3,3'-DMB induced also chromosome aberrations and exchange of sister chromatids in in vitro tests.

Although 3,3'-dimethylbenzidine is a derivative of carcinogenic benzidine, carcinogenic effects on humans have not been proven. However, research provides data about carcinogenic effect of 3,3'-DMB in animals. After subcutaneous administration of 3,3'-dimethylbenzidine and its dihydrochloride salt in drinking water, Zymbal's and mammary glands tumors, and cancers of uterus, skin, liver, hematopoietic system, small and large intestine were observed in rats. IARC classified 3,3'-dimethylbenzidine in the 2B group (a supposed carcinogenic agent for humans), whereas ACGIH – in the A3 group (proved carcinogenic effect on animals and unknown carcinogenic effect for humans). The European Union (according to the CLP classification) has listed 3,3'-DMB in the 1B category with the inscription "H350 – can cause cancer".

The permissible concentrations for 3,3'-dimethylbenzidine have been established in some European countries only (Austria, Slovenia and Switzerland) as 0.03 mg/m³.

The basis of the proposed maximum concentration value (MAC-TWA) for 3,3'-dimethylbenzidine and its salts was a risk assessment of cancer in male rats chronically exposed to 3,3'-dimethylbenzidine dihydrochloride in drinking water. Taking into account the cancer risk at the level of 10^-4, a concentration of 0.03 mg/m³ for the MAC-TWA value was proposed. There are no basis to determine the short-term value (STEL) and biological limit values (BLV). It was also proposed to label the compound with "Carc 1B", which indicates that it is a carcinogen category 1B, and "skin" – the absorption of substances through the skin may be as important as an inhalation route.

Chloroethene (vinyl chloride) is a large volume compound, which does not occur naturally in nature. It is obtained synthetically only. About 98% of all vinyl chloride production is used to produce polyvinyl chloride (PVC) and copolymers. Exposure to this compound occurs during the synthesis and polymerization, plastification and processing of polymers and copolymers. Vinyl chloride processing takes place in industries of plastics, footwear, rubber, pharmaceutical and other. In Poland, the total number of people exposed occupationally to this compound according to the data of the Chief Sanitary Inspectorate of 2015 is over 1300 people. Exposure of people to vinyl chloride can occur by inhalation, with water and food. Workers chronically exposed to high levels of vinyl chloride suffered from disease symptoms called vinyl chloride syndrome or disease, including headache and dizziness, blurred vision, fatigue, lack of appetite, nausea, insomnia, shortness of breath, stomach pain, pain in liver/spleen area. Clinical trials include rheumatoid changes of the skin, allergic dermatitis, acroosteolysis, peripheral polineuropathy, neurological disorders, and fibrosis of a liver, enlargement of spleen and liver, disturbances of porphyrins. Vinyl chloride has mutagenic/genotoxic properties. Vinyl chloride has been classified as a carcinogen by the International Agency for Research on Cancer, IARC (Group 1) and the European Union (Category 1.A).

The aim of this study was to develop and validate a sensitive method for determining concentrations of vinyl chloride in workplace air the range from 1/10 to 2 MAC values.

The study was performed using a gas chromatograph with mass spectrometry. The aim was to develop a method ensuring adequate determination of at least 1/10 NDS. Further considerations of the possibility of determining this substance in the air are based on previously developed analytical methods.

The use of the capillary INNOVAX column enables a selective determination of vinyl chloride in the presence of toluene, acetone and other co-existing compounds.

The detector's response to the analyzed chloroethene concentration was linear (r² = 0.9972) in the concentration range 1–26 μg / ml, which corresponded to the range of 0.20–5.2 mg/m³ (0.08–2 MAC value) for the a 5-L air sample. The limit of quantification (LOQ) of this method is 0.07 μg/ml. The developed method is precise, accurate and it meets the requirements of the European Standard No. PN-EN 482+A1: 2016 for procedures regarding the determination of chemical agents.

The developed method for determining vinyl chloride has been recorded as an analytical procedure (see appendix).

This article presents a method for measuring doxorubicin hydrochloride in workplace air with HPLC with diode array detector (DAD). The method is based on adsorption inhalable fraction of doxorubicin hydrochloride aerosol on glass fiber filter, desperation with water, and chromatographic analysis. The analysis was performed in reverse phase (mobile phase – 0.05 mol/L hydrophosphate disodum and acetonitrile (65:35) with pH – 3 with 0.5 mL/L triethylamine) on C18 column. The measurement range was 0.06 – 1 μg/m³ for 4800-L air sample. The limit of detection (LOD) was 0,0005 μg/ml and the limit of quantification (LOQ) was 0,0015 μg /ml. The developed method of doxorubicin hydrochloride determination has been recorded as an analytical procedure (see appendix).

1,2-Dichloroethane is a colorless, highly flammable liquid with a chloroform-like odor. This substance is used in industry as an intermediate in the production of vinyl chloride, but it is also used in the production of other chlorinated hydrocarbons. It is also used as a solvent. 1,2-Dichloroethane is carcinogenic for humans.

The aim of this study was to develop a method for determining concentrations of 1,2-dichloroethane in the workplace air in the range from 1/10 to 2 MAC values (0.82–16.4 mg/m³).

The study was performed using a gas chromatograph (GC) with a flame ionization detector (FID) equipped with a capillary column HP-1 (50 m x 0.32 mm; 0.3 μm).

The method is based on the adsorption of 1,2-dichloroethane on activated charcoal, desorption of analyzed compound with carbon disulfide and analysis of obtained solution with GC-FID. The use of HP-1 column enabled selective determination of 1,2-dichloroethane in a presence of other substances. The average desorption coefficient of 1,2-dichloroethane from charcoal was 0.98. The method is linear (r = 0.9999) within the investigated working range from 9.84 to 196.8 μg/ml, which is equivalent to air concentrations from 0.82 to 16.4 mg/m³ for a 12-L air sample. The limit of detection (LOD) and limit of quantification (LOQ) were to 2.284 μg/ml and 6.85 μg/ml, respectively.

The analytical method described in this paper enables selective determination of 1,2-dichloroethane in workplace air in presence of other substances at concentrations from 0.82 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 occupational exposure to 1,2-dichloroethane and associated risk to workers’ health.

The developed method of determining 1,2-dichloroethane has been recorded as an analytical procedure (see appendix).

Docetaxel (DCT) is a plant derived cytotoxic from taxane family – mitosis inhibitors. It is used in the treatment of breast, lung and prostate cancer, squamous cell carcinoma of the head and neck, and gastric adenoma. Docetaxel is a highly flammable liquid and health-threatening substance classified as mutagenicity category 2 and reproductive toxicity category 1B.

This paper presents a method for measuring docetaxel in the workplace air with HPLC with diode array detector (DAD). The method is based on the adsorption of inhalable fraction of docetaxel aerosol on glass fiber filter, desorption with water and chromatographic analysis. The analysis was performed in reverse phase on C18 column and mobile phase – acetonitrile: ammonium acetate solution (45: 55). The measurement range was 0.6 – 10 μg/m³ for 480-L air sample. The limit of detection (LOD) was 0.0065 μg/ml and the limit of quantification (LOQ) was 0.0195 μg/ml.

The developed method of docetaxel determination has been recorded as an analytical procedure (see appendix).

Etoposide at room temperature is a fine white to yellow-brown crystalline odorless powder. Etoposide is one of the most widely used cytotoxic drugs and has strong antitumour activity in cases of small-cell lung cancer, testicular cancer or lymphoma. Occupational exposure to etoposide (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 etoposide can cause suppression of bone marrow function and gastrointestinal symptoms such as nausea, vomiting, bronchospasm, inflammation of mucous membranes, hair loss and secondary leukemia. Agency for Research on Cancer (IARC) has classified etoposide as a compound probably carcinogenic to humans (Group 2.A) and in combination with cisplatin and bleomycin as carcinogenic to humans (Group 1).

The aim of this study was to develop and validate a sensitive method for determining inhalable fraction of etoposide 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 with tandem mass detection (HPLC-MS/MS). All chromatographic analysis were perfomed with Supelcosil LC 18 150 × 3 mm analytical column, which was eluted with a mixture of methanol and water with 0.1% of formic acid.

This method is based on collecting inhalable fraction of etoposide on glass fiber filter, extracting with a mixture of methanol: water with addition of formic acid (0.1%), and chromatographic determining of resulted solution with HPLC-MS/MS technique. The average extraction efficiency of etoposide from filters was 90%. The method is linear (r = 0.9985) within the investigated working range from 0.036 μg/ml to 1.44 μg/ml. The calculated limit of detection (LOD) and the limit of quantification (LOQ) were 0.0086 and 0.0026 μg/ml, respectively.

The analytical method described in this paper, thanks to HPLC MS/MS technique, enables specific and selective determination of inhalable fraction of etoposide in workplace air in the presence of other compounds at concentrations from 0.0001 mg/m³ (1/20 proposed MAC value). The method is precise, accurate and it meets the criteria for measuring chemical agents listed in Standard No. EN 482. The method can be used for assessing occupational exposure to etoposide and associated risk to workers’ health. The developed method of determining etoposide has been recorded as an analytical procedure (see appendix).