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Due to a potential exposure to several definite or probable carcinogens, the IARC classified manufacturing of art glass, glass containers, and pressed ware as probably carcinogenic to humans in 1993 (Group 2A). Purpose of this study was to update the evidence from recently published scientific reports. We searched for peer-reviewed articles published between 1993 and 2018 and combined result in terms of a meta-analysis. Overall, we considered twelve articles for a meta-analytic approach published after 1992. From a meta-analysis we derived a standardized incidence ratio (mSIR) and a standardized mortality ratio (mSMR) for lung cancer in men of 1.25 (95% CI 0.97–1.59) and 1.41 (95% CI 1.11–1.77), respectively. The estimated odds ratio (mOR) from five case–control studies was 1.25 (95% CI 0.90–1.73). Associated with an employment in glass factories, the estimated mSMR for larynx cancer was 2.38 (95% CI 1.23–4.16) based on two cohort studies; the mOR from four case–control studies was 1.35 (95% CI 0.73–2.52). Reports on elevated cancer risks at other sites were not consistent. Only few studies assessed cancer risk solely in glass workers. Gained evidence from more recent reports supports the IARC rating from 1993. Our combined results add limited evidence to a moderately elevated risk for cancer of the airways.

Objectives: Basal cell carcinoma (BCC) is mainly caused by high and long-term UV radiation. UV radiation causes DNA damage in various genes. Mutations of the p53 tumour suppressor gene have been identified in a wide variety of human cancers. The aim of the study was to analyse specific p53 mutations in BCCs in workers exposed to high and long-term UV radiation. Methods: The mutation pattern of the p53 tumour suppressor gene was analysed in tissue from 12 patients with UV-related BCC. All patients had a suspected occupational disease notified within the period 1995–1999. As a control, 20 BCC skin samples removed from areas definitively unexposed to sunlight were analysed. The specific mutations were determined by direct sequencing of codon 4 to 9 of the p53 gene in carcinomatous and adjacent non-neoplastic tissue after microdissection. Immunhistochemical analysis was performed to detect p53 protein. Results: p53 mutations were detected in 7/12 cases (58%). Point mutations were found in six cases (50%). In one case a deletion of 24 base pairs was observed. The most frequent mutations we found were CC→TT base-pair changes in four and C→T mutations in two cases. Within the control group specific p53 mutations were found in 11 cases (55%) without any C→T predominance. No case showed CC→TT mutations. Conclusions: Mutations of the p53 tumour suppressor gene in UV-associated BCC are frequent events. A predominance of C→T mutations and tandem CC→TT base-pair changes were observed in the sunlight-exposed cases only supporting the idea of site-directed mutagenesis by UV radiation in human BCC.

Objectives: Vinyl chloride (VC) and its metabolites are human carcinogens associated with liver angiosarcomas (LAS) and also with hepatocellular carcinomas (HCCs). In VC associated LAS mutations of the K-ras-2 gene have been reported; however, no data about the prevalence of such mutations in VC-associated HCCs are available. The aim of the study was to evaluate possible specific K-ras-2 oncogene mutations in the case of HCCs due to VC. Methods: The presence of K-ras-2 mutations was analysed in tissue from 12 patients with VC-associated HCCs. All patients had known long-term exposure to VC (average exposure amount: 9,942 ppm-years). Twenty patients with hepatocellular carcinoma due to hepatitis B (n=7), hepatitis C (n=5) and alcoholic liver cirrhosis (n=8) served as a control group. The specific mutations were determined by direct sequencing of codons 12 and 13 of the K-ras-2 gene in carcinomatous and adjacent non-neoplastic liver tissue after microdissection. Immunohistochemical analysis was performed to detect p21 ras protein. Results: K-ras-2 mutations were found in five of 12 (42%) examined HCCs and in three cases of adjacent non-neoplastic liver tissue (25%). There were three guanine to adenine (G → A) point mutations in the tumour tissue. All three mutations found in non-neoplastic liver from VC-exposed patients were also G → A point mutations (codon 12- and codon 13-aspartate mutations). Within the control group, K-ras-2 mutations were found in three of 20 (15%) examined HCCs. Conclusions: Mutations of the K-ras-2 gene in hepatocellular carcinomas associated with VC exposure are frequent events. We observed a K-ras-2 mutation pattern characteristic of chloroethylene oxide, one of the carcinogenic metabolites of VC analysed in animal models. Our results suggest that VC had direct toxic effects not only on endothelial cells but also on hepatocytes, as it was previously only described in animal models.

Objective. Carbon disulphide (CS2) is highly neurotoxic. There is ample evidence of damage to the peripheral and central nervous system. The air concentration at which such adverse effects can first be observed is presently a subject of controversy. Methods. In a cross-sectional study of CS2-exposed workers from the viscose industry and healthy controls, data on neurological complaints, basic laboratory diagnosis, clinical neurological examination and neuropsychological testing were evaluated. Data were from 222 workers in the viscose industry exposed to CS2 and 191 employees from the same factory with similar physical and psychological stress factors but without occupational contact with neurotoxic substances. Multiple linear or multiple logistic regression analysis was used to check for statistical differences. Results. The median of the CS2-measurements using personal air sampling was below the current maximum concentration permissible (MAK value) in Germany (10 ppm) in all departments. The threshold limit value was, however, exceeded in almost 10% of the persons investigated. Exposure fluctuated between

In a plant where flux-cored arc welding was applied to stainless steel, we investigated changes in airborne and internal metal exposure following improvements of exhaust ventilation and respiratory protection.Twelve welders were examined at a time in 2008 and in 2011 after improving health protection. Seven welders were enrolled in both surveys. Exposure measurement was performed by personal sampling of respirable welding fume inside the welding helmets during one work shift. Urine and blood samples were taken after the shift. Chromium (Cr), nickel (Ni), and manganese (Mn) were determined in air and biological samples.The geometric mean of respirable particles could be reduced from 4.1 mg/m(3) in 2008-0.5 mg/m(3) in 2011. Exposure to airborne metal compounds was also strongly reduced (Mn: 399 vs. 6.8 μg/m(3); Cr: 187 vs. 6.3 μg/m(3); Ni: 76 vs. 2.8 μg/m(3)), with the most striking reduction inside helmets with purified air supply. Area sampling revealed several concentrations above established or proposed exposure limits. Urinary metal concentrations were also reduced, but to a lesser extent (Cr: 14.8 vs. 4.5 μg/L; Ni: 7.9 vs. 3.1 μg/L). Although biologically regulated, the mean Mn concentration in blood declined from 12.8 to 8.9 μg/L.This intervention study demonstrated a distinct reduction in the exposure of welders using improved exhaust ventilation and welding helmets with purified air supply in the daily routine. Data from area sampling and biomonitoring indicated that the area background level may add considerably to the internal exposure.

Carbon disulphide (CS2), a reagent of rayon production, is known for its high toxic potential and has therefore been the subject of many clinical studies. The aims of the study presented here were to determine the effective exposure to CS2 and to compare the validity of the different exposure indicators. Internal and external exposure to CS2 was investigated in 362 male workers of a viscose factory. The CS2 air concentrations measured through stationary air monitoring in five different work areas (n = 39) were compared with the values of active personal air monitoring (n = 51) and passive personal air monitoring (n = 352). In addition, in all investigations biological monitoring was carried out by measuring the 2-thio-1,3- thiazolidine-carboxylic acid (TTCA) excretion in urine. A significant correlation was found between the data for active and passive personal air sampling (y = 0.99, x + 0.31, r = 0.968). The results of the stationary measurements led, however, to values which were systematically too low. The validity of TTCA excretion in urine as a parameter of biological monitoring could for the first time be verified in a large sample of subjects. There was a linear correlation between TTCA values in the urine related to both volume and creatinine [y (TTCAmg/g creatinine) = 0.315 x (ml CS2/m3 air) + 0.59] and the CS2 values in the air. Nevertheless, TTCA excretion proved to be dependent upon creatinine so that the excreted amounts related to creatinine described the individual exposure more exactly.

We report the application of a modified Edman degradation procedure to the analysis of benzene oxide adducts at the N-terminal valine of human hemoglobin (Hb). Benzene oxide is thought to be formed in the liver from benzene and adduct formation with macromolecules is therefore likely to occur. We assumed that benzene oxide could covalently bind to hemoglobin after leaving the hepatic tissue. The "N-alkyl Edman method" was adapted for the approach to investigate this hypothesis. Using capillary gas chromatography/mass spectrometry (GC/MS) with negative chemical ionization, we could not detect N-phenylvaline in blood samples from persons occupationally exposed to benzene. We conclude that adducts of benzene oxide to the N-terminal valine of Hb are not formed in detectable amounts in vivo and consequently are not suitable for biomonitoring purposes. This result clearly indicates that other reactive benzene metabolites have to be taken into account not only in the search for a biomarker but also as the ultimate carcinogenic species.

Fifty-three persons occupied in a municipal waste incinerator were examined with respect to their internal exposure to organic substances which may be produced during pyrolysis of organic matter. For this purpose the levels of benzene in blood, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in plasma, and mono- (MCPs), di- (DCPs), tri- (TCPs), tetra- (TCEPs) and pentachlorophenol (PCP) and hydroxypyrene in urine were determined. For control purposes, 431 men and women were examined. Significantly higher values for the workers were found for the excretion of hydroxypyrene [median (m): 0.24 vs 0.11 microgram/l; non-smokers], 2,4/2,5-DCP (m: 10.5 vs 3.9 micrograms/l) and 2,4,5-TCP (m: 1.2 vs 0.8 micrograms/l) and for the HCB level in plasma (m: 4.4 vs 2.8 micrograms/l). For the concentrations of 4-MCP and 2,3,4,6/2,3,5,6-TECP, the controls had significantly higher concentrations in urine than did the workers in the incineration plant (m: 4-MCP 1.7 vs 1.2; 2,3,4,6/2,3,5,6-TECP: 1.2 vs 0.3 micrograms/l). No significant differences between workers and controls were detected with respect to benzene in blood (m: 0.20 vs 0.28 microgram/l; non-smokers), 2,4,6-TCP and PCPs in urine (m: 0.85 vs 0.60 and 2.2 vs 2.2 micrograms/l) or the levels of PCB congeners in plasma (m: sigma 138, 153, 180: 5.6 vs 4.1 micrograms/l). The elevated levels of hydroxypyrene, 2,4/2,5-DCP, 2,4,5-TCP and HCB in biological material may be related to the incineration of the waste. These elevations, however, are very small and are of interest more from the environmental than from the occupational point of view.

Twenty-two persons (20 men and 2 women) were examined for their external and internal exposure to the glycol ether 1-methoxypropan-2-ol (PGME) during the production, leak testing and mounting of brake-hoses. For the measurement of external exposure, personal air monitoring was the method of choice. Average concentrations of PGME of 82.2 mg/m3 (22.3 ppm), 68.6 mg/m3 (18.6 ppm) and 11.3 mg/m3 (3.1 ppm) were found in the air of the brakehose production, leak test and mounting areas, respectively. For the estimation of internal exposure to PGME, this glycol ether was measured in both urine and blood. The biological samples were taken post-shift. The highest internal exposure levels were found in the brakehose production section and in the leak test area. The average post-shift concentrations for PGME in workers in the brakehose production section were 4.6 mg/l in urine and 13.5 mg/l in blood; the corresponding figures for workers in the leak test area were 4.2 mg/l in urine and 11.0 mg/l in blood. In blood and urine samples of workers engaged in the mounting area, PGME levels were below the detection limits. The elimination kinetics of PGME were also studied in three highly exposed persons, and mean excretion half-lives of PGME of approximately 4.4 h were found. On the basis of our results we made a rough calculation of a future biological tolerance value: we would except that concentrations of 38-109 mg per litre of blood and 10–31 mg per litre of urine would correspond to the German MAK value for PGME (375 mg/m3).

Seventeen persons (2 women and 15 men), who were exposed to glycolethers in a varnish production plant, were examined according to their external and internal solvent exposure. The workers in the production plant (n = 12) were exposed to average concentrations of ethoxyethanol, ethoxyethyl acetate, butoxyethanol, 1-methoxypropanol-2, 2-methoxypropyl-1-acetate and xylene of 2.8; 2.7; 1.1; 7.0; 2.8 and 1.7 ppm. In the air of the store (n = 3) and in the laboratory (n = 2) only minor concentrations of xylene respectively xylene and ethoxyethyl acetate could be measured. Internal exposure was estimated by measuring butoxyethanol (BE) in blood as well as ethoxyacetic acid (EAA) and butoxyacetic acid (BAA) in urine samples. Urine samples were taken pre- and post-shift. As expected, the highest values were found in the varnish production. The average post shift concentrations of BE, EAA and BAA were 121.3 micrograms/l; 167.8 and 10.5 mg/l. The relatively high concentrations of EAA and BAA in pre-shift samples can be explained by the long half-lives of these metabolites. According to our findings most of the glycolethers were taken up through the skin. Comparing our results with those reported in the literature we think that a future tolerable limit value for the concentration of ethoxyacetic acid in urine should be in the order of 100 to 200 mg/l.

Basis of the intercomparison programs for toxicological analyses in occupational and environmental medicine Intercomparison programs are intended to improve the reliability of laboratory results by objectively testing their accuracy under medical requirements. Such intercomparison programs are regulated in Germany by guidelines of the German Federal Medical Council. According to these guidelines, the supervisors of the intercomparison programs are responsible for the announcement, organization, and implementation of each intercomparison program and for the evaluation of the results. The supervisors are therefore scientifically responsible for the intercomparison programs that they organize and for the selection and testing of the suitability of the samples. Their suitability is tested, e.g., by the determination of reference values. The reference values and their tolerance ranges represent the target values for the participants in the intercomparison program. The supervisor awards the participants a certificate for successful participation in the intercomparison programs for each parameter within the tolerance range. The certificate is valid for 12 months. The guidelines for setting of the tolerance range are based both on the analytical conditions and the medical requirements. The medical requirements in the occupational-medical and environmental-medical range must be oriented to the valid reference intervals, and limits of decisions for medical evaluation and in the area of preventive medicine must be applied more strictly than in curative medicine. At least two intercomparison programs must be carried out per year, and for each analyte, two samples must be analyzed with diAerent concentration settings. The reference values are determined by reference laboratories [5, 6]. These laboratories are commissioned for toxicological analyses by the supervisor on the basis of their qualifications. These qualifications are apparent, e.g., from the observation that the laboratory or its head has evaluated methods for biological monitoring and published them in the international scientific literature. In addition, the laboratory should have successfully taken part in intercomparison programs organized by other institutions. Our laboratories take part in intercomparison programs in Canada, Finland, and Denmark and in the certification programs of the EU and the assignment programs for manufacturers of control materials (USA, Germany, and Norway). Also, the reference laboratories should routinely carry out toxicological analyses. A description of the requirements for reference laboratories has been published by Lehnert et al. [9] and by Angerer and Lehnert [2]. At present, 10 national and 14 international laboratories are commissioned to determine the reference values in the assurance program supervised by one of us (G.L.).