Biological Exposure Index Research Articles

Evaluation of Occupational Exposure to Perchlorethylene in a Group of Italian Dry Cleaners Using Noninvasive Exposure Indices.

Recent data suggest a general trend in decreased occupational exposure to perchlorethylene (PCE) in the dry-cleaning sector. The aims of this study were to confirm this trend to lower exposure levels in a group of Italian dry cleaners and to evaluate the current occupational PCE exposure in these works using noninvasive biological indices. Environmental exposure was assessed by personal sampling in 60 operators working in 21 dry cleaning shops in North Italy. PCE in the exhaled alveolar air (PCEalv), urinary concentration of PCE and of trichloroacetic acid (TCA) (PCEu and TCAu respectively), were measured as biological exposure indices. Median PCE environmental concentration in the whole sample was 10.6 mg/m3 (i.e., less than the 25% of the levels measured in the same area in a previous study). All values were less than 10% of the occupational limits. PCEu measured in samples collected at the end of the work shift resulted the biological markers having the strongest correlation with environmental PCE (r = 0.81). PCEalv also resulted in a high correlation (r = 0.66), while a lower correlation was found for TCAu measured at the end shift (r = 0.32). According to our results, PCEu can be proposed as a valid, noninvasive, and easily reliable exposure index to evaluate PCE exposure at the low levels currently observed in dry cleaners, therefore representing a promising alternative to invasive blood sample collections needed to determine PCE blood concentration.

Assessment of specific antibodies as biological indicators of human chronic exposure to microcystins.

Cyanobacteria can produce potent natural toxins known as cyanotoxins. Blooms of cyanobacteria, produced mainly as result of the pollution of water bodies with excessive amounts of phosphorus, represent a severe environmental problem; not only do they affect the normal equilibrium of the aquatic ecosystem but may also affect animal and human health. The occurrence of algal blooms have been increasing globally (it has been recently reported in at least 100 countries) and it has been considered by WHO as an emerging public health issue. The toxic effects of cyanotoxins have been thoroughly demonstrated in laboratory experiments, however, the effects on humans and the extent of these effects have been more difficult to assess. Epidemiological research is difficult as there are no specific symptoms or routine biomarkers to diagnose intoxication with cyanotoxins, in particular those cases associated with chronic exposure. The objectives of this study were to assess the exposure of a population settled near a lake with recurrent cyanobacteria blooms and to investigate the presence of biological markers of chronic exposure to cyanotoxins, in particular the microcystins (MCs). We first investigated the exposure of the population to cyanobacteria by using a questionnaire on how the population used the water and by analyzing water samples for the presence of cyanobacteria and total microcystins (TMCs). Secondly, we investigated the presence of biological indicators by analyzing the biochemical and immunological parameters in sera of the exposed population. The questionnaires and the water analyses revealed that the population under study (n = 47) is exposed to several exposure routes. The biochemical analyses of the sera showed the alteration of at least one hepatic enzyme in 25% of the exposed people, but this cannot be associated solely to MCs exposure. On the contrary, the immunological analyses, which included microcystin-LR specific antibodies IgE and IgG, showed significant differences between the exposed and non-exposed groups. The presence of MCs specific antibodies confirms the exposure to MCs. We propose the study of specific antibodies as a non-complex biomarker to detect chronic exposure to the toxin and to assist epidemiological studies.

Quantification of Urinary Metabolites of Toluene and Xylene Isomers as Biological Indices of Occupational Exposure in Printing Industry Workers

Background: In the printing industry, workers are occupationally exposed to an extensive variety of chemical solvents, including toluene and xylene. Biological monitoring is an essential tool for assessing occupational health risk. Objectives: The aim of the present study was to evaluate occupational exposure to toluene and xylene, as well as the biomarkers of exposure, in workers of the printing industry. Methods: The hippuric acid (HA) and o-, m- and p-methyl hippuric acids (o-, m-, p- MHAs) as the biomarkers of occupational exposure to toluene and each of the three xylene isomers, respectively, were determined in the urine samples of 84 subjects, including 44 printing workers and 40 non-exposed subjects. Results: The mean concentrations of toluene (37.64 ± 24.09 ppm) in the breathing zone of workers were higher, and the mean level of each of the three isomers of xylene (o-, m-, and p-xylene) was less than the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit values (TLVs). In addition, the levels of urinary HA, o-MHA, and m- and p-MHA in the exposed group were 0.15 ± 0.04, 0.11 ± 0.01, and 0.19 ± 0.07 g g-1 creatinine, respectively. Printing workers showed a significant increase in the levels of urinary HA compared to the non-exposed subjects (P < 0.001). The correlation analysis demonstrated significant correlations between the intensity of the occupational exposure to toluene and xylene and the level of exposure biomarkers in the urine. Conclusions: The results indicated that although all the urinary biomarkers of exposure were below the Biological Exposure Indices (BEIs) recommended by ACGIH, the levels of the urinary metabolites of toluene and xylene were increased in printing workers. Therefore, monitoring of occupational exposure to toluene and xylene is helpful in the following-up of affected workers in the printing industry.

Working Time Society consensus statements: Circadian time structure impacts vulnerability to xenobiotics-relevance to industrial toxicology and nonstandard work schedules.

The circadian time structure (CTS) has long been the subject of research in occupational medicine, but not to industrial toxicology, including methods of setting threshold limit values (TLVs) and employee biological monitoring. Numerous animal and human investigations document vulnerability to chemical, contagion, and other xenobiotics varies according to the circadian time of encounter. Permanent and rotating nightshift personnel are exposed to industrial contaminants in the same or higher concentration as dayshift personnel, and because of incomplete CTS adjustment to night work, contact with contaminants occurs during a different biological time than day workers. Thus, the amount of protection afforded by certain TLVs, especially for employees of high-risk settings who work night and other nonstandard shift schedules, might be inadequate. The CTS seems additionally germane to procedures of employee biological monitoring in that high-amplitude 24 h rhythms in biomarkers indicative of xenobiotic exposure may result in misjudgment of health risks when data are not gathered in sufficient frequency over time and properly interpreted. Biological reference values time-qualified for their rhythmic variation, currently of interest to laboratory medicine practice, are seemingly important to industrial medicine as circadian time and work-shift specific biological exposure indices to improve surveillance of personnel, particularly those working nonstandard shift schedules.

Polycyclic aromatic hydrocarbons as a potential source of carcinogenicity of mate

Drinking mate, an infusion of the herb ilex paraguariensis, is very common in several South American countries, and has been associated with an increased risk of esophageal cancer. This increased risk may be attributed to drinking mate very hot, or to mate’s potentially carcinogenic contaminants, such as polycyclic aromatic hydrocarbons (PAHs). Mate leaves are often dried via smoking, and therefore commercial samples may have high amounts of PAHs. We found 10 original articles that had measured PAHs in commercial dry samples, and nearly all found very high mass fractions. Most studies found benzo[a]pyrene mass fractions to be over 25 ng/g, and some found levels up to 600 ng/g. However, carcinogenic PAHs are often hydrophobic, and may not readily transfer into infusions. Seven articles studied transfer rates, and these rates varied from 1 to 50%, depending on the methods employed. Further careful studies of transfer rates in situations that mimic real life drinking of mate are recommended. Also, further studies of biological indicators of PAH exposure, particularly in randomized experiments, and analyzing DNA from tumor samples of mate drinkers are recommended.

Buta-1,3-diene. Documentation of proposed values of occupational exposure limits (OELs)

Buta-1,3-diene is a gas used in the production of thermoplastic resins, elastomers and synthetic rubber. Buta-1,3-diene is absorbed mainly in the respiratory tract and then metabolized to monoepoxide – 1,2-epoxybut-3-ene and diepoxide – 1.2:3,4 diepoxybutane, and after their conjugation with glutathione is excreted with urine. According to data from the Central Registry on Exposure to Substances, Mixtures, Agents or Carcinogenic or Mutagenic Technological Processes, in 2015 the number of people exposed to buta-1,3-diene in Poland was 958 and additionally about 200 were exposed to petroleum substances which carcinogenic effect is depending on the buta-1,3-diene. According to data from sanitary-epidemiological stations, in Poland in 2013 and 2016, there were no workers exposed to buta-1,3-diene at levels exceeding maximum allowable concentration (MAC) of 4.4 mg/m3. Buta-1,3-diene in small concentrations is a mild narcotic agent for humans, while for occupationally exposed workers it has irritating properties to the mucous membranes of the eyes and airways. Buta-1,3-diene is a substance with low acute toxicity to animals (LC50 value for rats is 270 000 mg/m3). This substance is mutagenic and genotoxic, it can cause damage to the genetic material of somatic and germ cells. It has been proved that buta-1,3-diene is carcinogenic for B6C3F1 mice and rats. There is also epidemiological evidence that occupational exposure to buta-1,3-diene is associated with the risk of a cancer of a lymphohematopoietic system. According to the IARC classification, buta-1,3-diene is included in group 1, i.e., carcinogenic substances for humans, and according to ACGIH classification to group A2, i.e., substances suspected to be carcinogenic for humans. In Europe, buta-1,3-diene is classified in Cat. 1A. carcinogens and Cat. 1B. mutagenic compounds. Buta-1,3-diene does not cause fertility disturbances, and its teratogenic effects appeared when doses were toxic to mothers only. In Directive 2017/2398 of the European Parliament and of Council (EU) 2017/2398 of 12 December 2017 amending Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work for buta-1,3-diene, binding occupational exposure limit value (BOELV ) was at the level of 2.2 mg/m3 (Official Journal of the EU L 345 of 27/12/2017, p. 87). The directive will be in force in the EU Member States on January 17, 2020. It was proposed to adopt the value of the maximum allowable concentration (MAC) of the buta-1,3-diene at the level of 2.2 mg/m3 and the following values of the biological exposure indices (BEI):  1.6 mg of 1,2-dihydroxy-4-(N-acetyl-cystein-S-yl)butane/g creatinine in urine measured at the end of working shift  2.1 pmol/g Hb - hemoglobin adducts: mixture of N-[1-(hydroxymethyl)prop-2-enyl]valine and N (2-hydroxybut-3-enyl)valine in blood showing exposure for the last 120 days. This standard is additionally marked Carc. 1A – a substance with proven carcinogenic effect for humans and Muta. 1B – a substance that is considered mutagenic for humans. There is no evidence for establishing STEL value for buta-1,3-diene. The estimated additional risk of leukemia during the 40-year exposure to buta-1,3-diene at a concentration of 2.2 mg/m3 is 8×10-7, it is lower than the risk for the general population in Poland, which is 7.15×10-5.

O-Toluidine. Documentation of proposed values of occupational exposure limits (OELs)

o-Toluidine is a substance produced in large amounts and used in rubber, dyeing and pharmaceutical industries and in the production of herbicide and other chemical compounds. The estimated number of people occupationally exposed to o-toluidine in EU is 5500, half of them is employed in chemical industry in the production of chemical fibers and rubber products. In the conditions of occupational exposure, o-toluidine is absorbed by skin and by inhalation. Regardless of route of exposure this compound is excreted in urine. The effects of acute inhalation exposure to high concentrations (&gt;25 mg/m3) of o-toluidine are irritation of upper respiratory tract, irritation of eyes and skin, which is manifested by face, eyes and pharynx burning, cough, shortness of breath, weakness, nausea, vomit, headache and dizziness, tinnitus, methemoglobinemia, hematuria and hemorrhagic cystitis. In epidemiological studies, the mostly analyzed group of substances was aromatic amines (including o-toluidine). Available data mainly refer to exposure in dyeing and rubber industries. Described effects of chronic exposure are methemoglobinemia, hematuria and damage of bladder epithelium leading to malignant tumor of this organ. Carcinogenicity of o-toluidine was confirmed in tests on experimental animals, including rats and mice. Oral exposure to o-toluidine results in bladder cancer, primarily in female rats, to a lesser extent in male rats. In female rats F344 exposed to o-toluidine with feed, increase of the incidence of cancer from the bladder transitional cells was observed. Furthermore, in mice and rats fibromas and fibrosarcomas in subcutaneous tissue, angiomas and angiosarcomas in abdominal cavity and bladder, mesotheliomas of various organs, angiosarcomas in various organs, hepatocellular carcinomas and adenomas were observed. In experimental animals, o-toluidine exhibits moderate acute toxicity, LD50 values for intragastric administration are within the range 670–2951 mg/kg bw. In acute toxicity studies, rats exposed by inhalation to o-toluidine had cyanosis, contractions and muscle tremor, difficulty in breathing, red-brown rhinorrhea, corneal opacification, body weight loss, body temperature decrease, lethargy and extreme exhaustion. The effects of subchronic and chronic exposure of experimental animals to o-toluidine described in the literature include changes in the spleen, hematopoietic system, kidneys and bladder. Most of the mutagenicity tests in bacterial systems do not confirm mutagenicity of o-toluidine. A few works only described positive test result after metabolic activation. Both in vitro and in vivo studies confirmed induction of DNA damage by o-toluidine. o-Toluidine has harmonized classification in the EU as a category 1B carcinogen with assigned phrase H350 – may cause cancer. SCOEL experts classified it to group A of carcinogens, which means carcinogens with genotoxic properties. In Germany, DFG has ranked o-toluidine into category 1 of carcinogens, so substances that cause cancer in humans and substances that are believed to significantly affect the risk of cancer. IARC classified it into group 1, compounds with confirmed human carcinogenicity. On the basis of a quantitative assessment of the risk of cancer as a result of occupational exposure, it has been estimated that at a 40-year exposure period to o-toluidine at a concentration of 1 mg/m3, the additional risk of bladder cancer ranges from 2.4–3.1 · 10-4 (depending on the estimation method). The values of the determining exposure limits of o-toluidine applicable in the EU member states and in the world are 0.5–0.9 mg/m3; 4.5–8.8 mg/m3 and 22 mg/m3. In Poland, the applicable OEL value is 3 mg/m3. In SCOEL, no BOELV had been proposed, considering o-toluidine as a genotoxic carcinogen. Directive 2017/2398 of the European Parliament and of the Council (EU) of 12 December 2017 amending Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work, a concentration of 0.5 mg/m3 was adopted (0.1 ppm) as a binding value for o-toluidine (based on socio-economic analysis, environmental risk assessment and risk of bladder cancer in professionally exposed workers). It has been proposed to reduce the OEL value of o-toluidine to 0.5 mg/m3, which will affect a nearly tenfold reduction in the risk of bladder cancer workers. In addition, according to CSI (Chief Sanitary Inspectorate) data in Poland, no exposure to o-toluidine in concentrations &gt;3 mg/m3 and &gt;1.5 mg/m3 (0.5 OEL values) have been found in years 2015–2016, while in conditions of exposure to concentrations from within the range of 0.3–1.5 mg/m3 (0.1 ÷ 0.5 of the OEL value), a dozen or so people only worked. There is no basis for determining the short-term exposure limit value (STEL). As a value of biological exposure index (BEI) of o-toluidine, it has been proposed to leave 2% level of the MetHb in the blood. The standard was labeled “skin” (the absorption of substances through the skin may be as important as in inhalation) and “Carc. 1B” (carcinogenic substance of category 1B).

Buta-1,3-diene. Documentation of proposed values of occupational exposure limits (OELs)

Buta-1,3-diene is a gas used in the production of thermoplastic resins, elastomers and synthetic rubber. Buta-1,3-diene is absorbed mainly in the respiratory tract and then metabolized to monoepoxide – 1,2-epoxybut-3-ene and diepoxide – 1.2:3,4 diepoxybutane, and after their conjugation with glutathione is excreted with urine. According to data from the Central Registry on Exposure to Substances, Mixtures, Agents or Carcinogenic or Mutagenic Technological Processes, in 2015 the number of people exposed to buta-1,3-diene in Poland was 958 and additionally about 200 were exposed to petroleum substances which carcinogenic effect is depending on the buta-1,3-diene. According to data from sanitary-epidemiological stations, in Poland in 2013 and 2016, there were no workers exposed to buta-1,3-diene at levels exceeding maximum allowable concentration (MAC) of 4.4 mg/m3. Buta-1,3-diene in small concentrations is a mild narcotic agent for humans, while for occupationally exposed workers it has irritating properties to the mucous membranes of the eyes and airways. Buta-1,3-diene is a substance with low acute toxicity to animals (LC50 value for rats is 270 000 mg/m3). This substance is mutagenic and genotoxic, it can cause damage to the genetic material of somatic and germ cells. It has been proved that buta-1,3-diene is carcinogenic for B6C3F1 mice and rats. There is also epidemiological evidence that occupational exposure to buta-1,3-diene is associated with the risk of a cancer of a lymphohematopoietic system. According to the IARC classification, buta-1,3-diene is included in group 1, i.e., carcinogenic substances for humans, and according to ACGIH classification to group A2, i.e., substances suspected to be carcinogenic for humans. In Europe, buta-1,3-diene is classified in Cat. 1A. carcinogens and Cat. 1B. mutagenic compounds. Buta-1,3-diene does not cause fertility disturbances, and its teratogenic effects appeared when doses were toxic to mothers only. In Directive 2017/2398 of the European Parliament and of Council (EU) 2017/2398 of 12 December 2017 amending Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work for buta-1,3-diene, binding occupational exposure limit value (BOELV ) was at the level of 2.2 mg/m3 (Official Journal of the EU L 345 of 27/12/2017, p. 87). The directive will be in force in the EU Member States on January 17, 2020. It was proposed to adopt the value of the maximum allowable concentration (MAC) of the buta-1,3-diene at the level of 2.2 mg/m3 and the following values of the biological exposure indices (BEI): • 1.6 mg/g creatinine of 1,2-dihydroxy-4-(N-acetyl-cystein-S-yl)butane in urine measured at the end of working shift • 2.1 pmol/g Hb - hemoglobin adducts: mixture of N-[1-(hydroxymethyl)prop-2-enyl]valine and N (2-hydroxybut-3-enyl)valine in blood showing exposure for the last 120 days. This standard is additionally marked Carc. 1A – a substance with proven carcinogenic effect for humans and Muta. 1B – a substance that is considered mutagenic for humans. There is no evidence for establishing STEL value for buta-1,3-diene. The estimated additional risk of leukemia during the 40-year exposure to buta-1,3-diene at a concentration of 2.2 mg/m3 is 8×10-7, it is lower than the risk for the general population in Poland, which is 7.15×10-5.

Exposure to Cadmium and Lead in Cigarette Smokers Who Switched to Electronic Cigarettes.

Electronic cigarettes (ECs) seem to be a less harmful alternative for conventional cigarettes. This study aimed to assess whether the generated aerosols from ECs contain lower amount of cadmium (Cd) and lead (Pb) than cigarette smoke and to detect any changes in exposure to Cd and Pb among cigarette smokers who switched completely or partially to EC. EC aerosols and cigarette smoke were generated, and the determination of Cd and Pb in trapped samples and e-liquids was performed by the electrothermal atomic absorption spectrometry method. A cross-sectional, group-based survey was carried out using 156 volunteers classified into groups of nonsmokers, EC-only users, dual EC users-cigarette smokers, and cigarette-only smokers. Using electrothermal atomic absorption spectrometry, blood Cd and Pb levels were measured, and the results were compared by analysis of covariance. Transfer of Cd and Pb to EC aerosol was found to be minimal, although the metals were present in the remaining e-liquid from tanks used for vapor generation. The geometric mean blood Cd concentration adjusted for age and sex was 0.44 (95% confidence interval = 0.37 to 0.52) µg/L in the EC-only users, which was significantly lower than those in the smokers of 1.44 (1.16 to 1.78) and dual users of 1.38 (1.11 to 1.72). The blood Pb geometric mean differed significantly only between nonsmokers of 11.9 (10.6 to 13.3) and smokers of 15.9 (13.6 to 18.6). The study revealed that smokers who completely switched to ECs and quit smoking conventional cigarettes may significantly reduce their exposure to Cd and probably Pb. Switching to EC use is associated with a rapid and substantial decrease in the exposure to carcinogenic Cd. Exposure to Pb is probably also decreased but may be overshadowed by other factors. The study provides empirical data based not only on the analysis of generated aerosol but also on biological indicators of recent exposure-that is, the concentrations of Cd and Pb in blood, indicating EC as a potential harm-reduction device, especially regarding Cd exposure. However, in this case, dual EC use-cigarette smoking provides doubtful benefits.

EXPOSICIÓN A BENCENO EN UNA POBLACIÓN INFANTIL URBANA DEL NORESTE DE MÉXICO

The aim of this study was to assess the benzene exposure levels in children living in Cadereyta Jimenez in Nuevo Leon state, through determination of urinary trans, trans-muconic acid, a biomarker of benzene exposure. Our results shown that 28 % of the population exceeds the biological exposure index (500 µg/g CR). Considering that benzene is related with hematological malignances it is necessary to undertake studies to assess hematological risks in children living in areas with petrochemical activity.

Evaluation of the Suitability of Establishing Biological Exposure Indices of Styrene.

BackgroundThis study was designed to provide logical backgrounds for the revision of biological exposure indices (BEIs) for styrene exposure in Korea. In order to investigate the correlation between airborne styrene and biological exposure indices, we measured urinary mandelic acid (MA) and phenylglyoxylic acid (PGA) in workers exposed to styrene occupationally, as well as airborne styrene at workplaces.MethodsSurveys were conducted for 56 subjects. The concentrations of airborne styrene and urinary metabolites of styrene were measured in 36 workers who were occupationally exposed to styrene, and in 20 controls. Air samples were collected using personal air samplers and analyzed by gas chromatography. Urine samples were collected at the end of the shift and analyzed by high performance liquid chromatography.ResultsThe geometric mean concentration of airborne styrene was 9.6 ppm. The concentrations of urinary MA, PGA, and MA+PGA in the exposure group were 267.7, 143.3, and 416.8 mg/g creatinine, respectively. The correlation coefficients for correlation between airborne styrene and MA, PGA, and MA+PGA were 0.714, 0.604, and 0.769, respectively. The sum of urinary MA and PGA corresponding to an exposure of 20 ppm styrene was 603 mg/g creatinine.ConclusionThe correlation of the sum of urinary MA and PGA with airborne styrene was better than the correlation of each individual urinary determinant. It is considered appropriate to amend the concentration of urinary MA+PGA to 600 mg/g creatinine as a BEI, which corresponds to an airborne styrene concentration of 20 ppm in Korea.

Potassium bromate – inhalable fraction. Documentation of proposed values of occupational exposure limits (OELs)

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

Assessing exposure to metals using biomonitoring: Achievements and challenges experienced through surveys in low- and middle-income countries

In this narrative account based on a keynote presentation on exposure biomonitoring of metals in low- and middle-income countries (LMIC), we first briefly address practical issues that have arisen from our experience during the conduct of various surveys in LMIC. These have included the statistical handling of multiple pollutants in the same subject, the problem of correctly adjusting for urinary flow in spot samples of urine, and the possible external contamination of samples when doing field surveys in challenging environments.We then review and present selected results from surveys conducted in the mining area of Katanga in the Democratic Republic of Congo (DR Congo), where we documented high urinary levels of cobalt and other trace metals (arsenic, uranium) in people living close (<3 km) to mining or smelting operations (Banza et al., 2009). Consumption of contaminated foodstuffs (maize, legumes, fish) and, especially among children, dust ingestion proved to be the main sources of exposure to cobalt (Cheyns et al., 2014). Urinary biomonitoring studies among artisanal workers involved in mining cobalt, craftsmen working malachite, and workers processing gold ore revealed high to extremely high values of cobalt (largely exceeding the Biological Exposure Index of 15 μg/L), as well as other trace metals such as uranium, manganese, lead or mercury, depending on the type of jobs.This abundant biomonitoring data has been valuable to argue for improved enforcement of legislation to protect workers and citizens against the hazards posed by the mining activities in the area. Epidemiological studies have been undertaken and are ongoing to assess the human health impact of this pollution.

Occupational Exposure to Metals in Shooting Ranges: A Biomonitoring Study.

BackgroundLead (Pb) exposure in shooting ranges has been reduced by various measures such as jacketed ammunition and lead-free primers. Nevertheless, this may lead to exposure to other metals, potentially resulting in adverse health effects.MethodsIn a cross-sectional study, 35 subjects from seven different shooting ranges were studied: four shooting instructors, 10 police officers, 15 Special Forces, and six maintenance staff members. Metals and metalloids were determined in blood and urine by inductively coupled plasma–mass spectrometry.ResultsThe concentrations of most elements did not differ significantly between groups or compared to reference values, except for Sb and Pt in urine and Pb in blood. Mean values for Sb were considerably higher in urine from the Special Forces (0.34 μg/L), the maintenance staff (0.13 μg/L), and shooting instructors (0.32 μg/L) compared to the police officers before shooting (0.06 μg/L) and a Belgian reference value (0.04 μg/L). For Pt, the Special Forces showed higher mean urinary concentrations (0.078 μg/L) compared to a Belgian reference value (<0.061 μg/L). Mean values for blood lead were markedly higher in the Special Forces (3.9 μg/dL), maintenance staff (5.7 μg/dL), and instructors (11.7 μg/dL) compared to police officers (1.4 μg/dL). One instructor exceeded the biological exposure index for blood Pb (38.8 μg/dL).ConclusionSince both Pb and Sb were found to be higher in shooting range employees, especially among frequent shooters, it is advisable to provide appropriate protective equipment, education, and medical follow-up for shooting range personnel in addition to careful choice of ammunition.

On the diagnosis of malignant pleural mesothelioma: A necropsy-based study of 171 cases (1997-2016).

Malignant pleural mesothelioma (MPM) diagnosis is known to be difficult. We report on the diagnostic elements available in life in an MPM necropsy case series and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices. We reviewed pathologic and clinical records of an unselected series of autopsies (1977-2016) in patients with MPM employed in the Monfalcone shipyards or living with shipyard workers. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings, with and without immunophenotyping. Data on 171 cases were available: for 169, autopsy confirmed the MPM diagnosis. In life, 119 cases had histologic confirmation of diagnosis, whereas 7 were negative; all cases without immunophenotypization were autoptic MPMs. Cytology alone had been positive in 18 autoptic MPM cases, negative in 14. Radiologic imaging alone had been positive in another 16, negative in 11. In the 2 cases not confirmed at autopsy, MPM had been suspected by chest computed tomography only. Bilateral pleural plaques were found in 144 and histologic evidence of asbestosis in 62 cases. Autopsies confirmed 169/171 cases, including cases that would not be considered as certain based on diagnosis in life. Radiologic imaging, cytologic examination of pleural effusions, or both combined had low sensitivity but high positive predictive value: when they are positive, proceeding to thoracoscopy should be justified. MPM has been correctly diagnosed even without immunohistochemistry. The prevalence of pleural plaques and asbestosis was high due to severity of asbestos exposures in these cases.

Biological Monitoring and Lung Function Assessment among Workers Exposed to Chromium in the Ceramic Industry.

Chromium exposure occurs in various industries such as ceramics industry. The main disadvantage of chromium is high toxicity when absorbed by the body. This study aimed to determine and compare urinary chromium values in the pre- and post-shift of ceramic glazers and the control group; investigate urinary chromium value according to the study variables; compare pulmonary function tests between ceramic glazers vs. the control group. A cross-sectional study. This study was carried out in Yazd City, central Iran on 49 glazers and 55 office workers in the same workplace as the control group. The urine samples were collected at both start and end of the work shift, and the control group was examined only once. Preparation of samples were conducted by Solid Phase Extraction (SPE). The analyses were performed by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). All the participants filled out a self-administered questionnaire comprising of questions about smoking habits, work shift, skin dermatitis, job title, using mask, ventilation system, duration of exposure, overtime working, age, weight, and height. The lung function tests were performed on study groups. The concentration of chromium after the glazer's shift was 2.73 times higher than the Biological Exposure Index (BEI) recommended by the occupational and environmental health center of Iran. Lung function tests were significantly lower in the glazers compared with the control group (P=0.001). Skin dermatitis and overtime working are the main determinants of high chromium level in glazers.

Gene Expression as a Dosimeter in Irradiated Drosophila melanogaster.

Biological indicators would be of use in radiation dosimetry in situations where an exposed person is not wearing a dosimeter, or when physical dosimeters are insufficient to estimate the risk caused by the radiation exposure. In this work, we investigate the use of gene expression as a dosimeter. Gene expression analysis was done on 15,222 genes of Drosophila melanogaster (fruit flies) at days 2, 10, and 20 postirradiation, with X-ray exposures of 10, 1000, 5000, 10,000, and 20,000 roentgens. Several genes were identified, which could serve as a biodosimeter in an irradiated D. melanogaster model. Many of these genes have human homologues. Six genes showed a linear response (R2 > 0.9) with dose at all time points. One of these genes, inverted repeat-binding protein, is a known DNA repair gene and has a human homologue (XRCC6). The lowest dose, 10 roentgen, is very low for fruit flies. If the lowest dose is excluded, 13 genes showed a linear response with dose at all time points. This includes 5 of 6 genes that were linear with all radiation doses included. Of these 13 genes, 4 have human homologues and 8 have known functions. The expression of this panel of genes, particularly those with human homologues, could potentially be used as the biological indicator of radiation exposure in dosimetry applications.

Design of a calix[4]arene-functionalized metal-organic framework probe for highly sensitive and selective monitor of hippuric acid for indexing toluene exposure

In the present work, a novel metal-organic framework (MOF) fluorescent probe was prepared by post-synthetic modification of MIL-53-NH2(Al) with carboxylatocalix[4]arene (CC[4]A). The introduced CC[4]A could not only enhance the fluorescence performance and the recognition ability of the probe, but also sustain the high stability under UV light and moisture conditions. A method based on the as-synthesized CC[4]A@MIL-53-NH2(Al) probe was established for sensing hippuric acid. The detection limit was determined to be as low as 3.7 μg mL−1. Over the concentration range of 0.005–3 mg mL−1, the calibration curve was obtained with a satisfactory linearity (R2 = 0.993). The method was successfully used for rapid and highly selective direct monitor of hippuric acid in human urine. The sensor had great potential to be used as a simple diagnostic tool for hippuric acid in human urine which is regarded as a biological index of toluene exposure.

Urea – inhalable fraction. Documentation of proposed values of occupational exposure limits (OELs)

Urea is a non-flammable, colorless or white crystalline solid. It has a faint aroma of ammonia and a cooling, saline taste. It is hygroscopic, very well soluble in water. During long-term storage and in aqueous solutions urea partly decomposes with the release of ammonia and carbon dioxide. Urea is used as a: component of fertilizer and animal feed; raw material for production of plastics, flame-proofing agents, adhesives, medicines, cosmetics and household products; reductant in selective catalytic reduction (SCR) systems used to reduce NOx emissions from stationary and mobile sources; deicing compound on roads, railroad tracks and airport runways; in the food industry as an additive for bakery products, alcoholic beverages and gelatine-based products and as a reagent in laboratories. In 2012, world production of urea was estimated to be around 184 million tonnes and is projected to increase further. In the European Chemicals Agency, urea was registered by 5 companies from Poland. The number of workers exposed to urea in 2 of these plants is a total of 201 people. Urea is an endogenous product, formed in the liver in the urea cycle from ammonia formed by the catabolism of amino acids and proteins, is then excreted by the kidneys. An adult man excretes about 20 ÷ 35 g of urea in the urine during the day. Most of the information on the effects of urea in humans comes from patients with renal insufficiency who have elevated urea levels. Adverse effects of urea include: headache, nausea, vomiting, syncope, confusion, electrolyte abnormalities in the blood. Urea has a slight irritating effect on the eyes and does not irritate the skin. At concentrations above 10% urea has a keratolytic effect - it facilitates peeling and increases the permeability of the stratum corneum, thereby increasing the therapeutic activity of many topical medications. Based on animal studies urea has low acute and chronic toxicity and no carcinogenic or reproductive toxicity. Urea does not meet the classification criteria as a CLP hazardous substance. Due to very low vapor pressure, exposure is possible only to urea dust. Therefore, in order to protect workers from the nuisance of particulate matter (dust) of urea, the MAC (TWA) value of 10 mg/m3 was recommended as for other dusts not classified for toxicity but posing a hazard for visibility reasons. There is no basis for determining the short-term exposure limit value (STEL) and the biological exposure index value (BEI).

Gestational exposure to volatile organic compounds (VOCs) in Northeastern British Columbia, Canada: A pilot study

BackgroundNortheastern British Columbia (Canada) is an area of intense hydraulic fracturing for unconventional natural gas exploitation. There have been multiple reports of air and water contamination by volatile organic compounds in the vicinity of gas wells. Although these chemicals are known developmental toxicants, no biomonitoring effort has been carried out in the region. ObjectiveTo evaluate gestational exposure to benzene and toluene in the Peace River Valley, Northeastern British Columbia (Canada). MethodsUrine samples were collected over five consecutive days from 29 pregnant women. Metabolites of benzene (s-phenylmercapturic acid (S-PMA) and trans, trans-muconic acid (t,t-MA)) and toluene (s-benzylmercapturic acid (S-BMA)) were measured in pooled urine samples from each participant. Levels of benzene metabolites were compared to those from the general Canadian population and from a biomonitoring study of residents from an area of active gas exploitation in Pavillion, Wyoming (USA). Levels measured in participants from the two recruitment sites, and self-identifying as Indigenous or non-Indigenous, were also compared. ResultsWhereas the median S-PMA level (0.18μg/g creatinine) in our study was similar to that in the general Canadian population, the median t,t-MA level (180μg/g creatinine) was approximately 3.5 times higher. Five women had t,t-MA levels above the biological exposure index® proposed by the American Conference of Governmental Industrial Hygienists. The median urinary S-BMA level in our pilot study was 7.00μg/g creatinine. Urinary metabolite levels were slightly higher in self-identifying Indigenous women, but this difference was only statistically significant for S-PMA. DiscussionUrinary t,t-MA levels, but not S-PMA levels, measured in our study are suggestive of a higher benzene exposure in participating pregnant women from the Peace River Valley than in the general Canadian population. Given the small sample size and limitations of t,t-MA measurements (e.g., non-specificity), more extensive monitoring is warranted.