Characterisation of exposure to total and hexavalent chromium of welders using biological monitoring.

Inhalation exposure to total and hexavalent chromium (TCr and HCr) was assessed by personal air sampling and biological monitoring in 53 welders and 20 references. Median inhalation exposure levels of TCr were 1.3, 6.0, and 5.4 microg/m(3) for welders of mild steel (MS, <5% alloys), high alloy steel (HAS, >5% alloys), and stainless steel (SS, >26% alloys), respectively. The median exposures to HCr compounds were 0.23, 0.20, and 0.08 microg/m(3), respectively. Median concentrations of TCr in urine, blood plasma and erythrocytes were elevated in all welders, compared with the corresponding median concentrations in the reference group (p<0.005). The TCr levels observed in plasma were two-fold higher in welders of SS and HAS than in welders of MS (p<0.01). Exposure to HCr as indicated by median total content of Cr in erythrocytes was 10 microg/L in welders of SS, MS and HAS. Uptake of TCr during the shift was confirmed for welders of SS by a median increase of urinary TCr from pre- to post-shift of 0.30 microg/g creatinine. For welders of MS and HAS as a group TCr was not increased.

New applications of biological monitoring for environmental exposure and susceptibility monitoring. Report of the 7th International Symposium on Biological Monitoring in Occupational and Environmental Health.

Validated biological monitoring methods are used in large-scale monitoring programmes involving determination of ubiquitous environmental pollutants such as metals and pesticides. Some programmes focus on children's exposure, and policies to prevent adverse health effects. Most of these initiatives are aimed at characterizing trends. Some of these programmes are designed to investigate the role of certain exposures in disease. Fewer new biological monitoring methods were presented during the present meeting than in previous meetings. All of these new methods used mass spectrometric-based detection and quantification. There is an increasing use of biomarkers to study genetic polymorphisms of enzyme systems involved in both toxification pathways and metabolite conjugation and DNA repair. At the meeting a discussion was started that could lead to a further harmonization of the scientific fundaments of the use of biological monitoring in occupational health with possible value also for applications in the field of environmental health.

Carcinogenicity study of outdoor airborne particulate matter in newborn male NMRI mice.

An organic extract of airborne particulate matter (APM) was tested for carcinogenicity at two dose levels in the newborn mouse bioassay. The samples used were taken under specific polluted conditions. The doses tested corresponded with 0.75 and 1.5 times the amount of air man inhales during lifetime. Benzo(a)pyrene, which was used as a positive control, significantly increased the lung tumor incidence. No evidence was found for a carcinogenic activity of the organic extract of APM. Considering the high dose of APM applied in this animal model and the much lower actual cumulative dose to which man is exposed to in many areas, the conclusion can be drawn that exposure to APM alone probably does not represent an important cancer risk for man.

Effects of outdoor and indoor airborne particulate matter on thyroid hormone and vitamin A metabolism.

Vitamin A is an important regulator of normal epithelial differentiation and proliferation and might act in the promotion phase of carcinogenesis. Vitamin A and thyroid hormone metabolism are linked by a common plasma carrier protein transthyretin (TTR). Results indicated that extracts of outdoor and indoor airborne particulate matter (APM), originating from different pollution sources, significantly interfered with thyroxine (T4) binding to TTR. The neutral fraction accounted for most of the inhibitory activity. Polycyclic aromatic hydrocarbons and nitrated derivatives were not responsible for the activity of the neural fraction. A single treatment of rats with an outdoor and cigarette smoke APM extract depleted plasma T4 and triiodothyronine levels and increased plasma retinol levels, while liver and lung retinol levels were depleted. The studies show that APM extracts have the potency to interfere with thyroid hormone metabolism both in vitro and in vivo and to deplete lung vitamin A in vivo.

Inhibition of gap-junctional intercellular communication by outdoor and indoor airborne particulate matter.

The inhibition of gap-junctional intercellular communication (GJIC) by different airborne particulate matter (APM) extracts was tested in V79 cells and in primary cultures of alveolar type II cells. The results show that extracts of APM were able to inhibit GJIC in V79 and in alveolar type II cells at non-cytotoxic doses. Chemical fractionation of extracts showed that the neutral fractions accounted for most of the inhibitory activity on GJIC. The activities of basic and acid fractions was less than 5% of the total activity. Polycyclic aromatic hydrocarbons and nitrated derivatives are unlikely to be responsible for the activity of the neutral fractions, because several representatives of these compounds failed to inhibit GJIC. Taken together, these results suggest that extracts of APM, in addition to the genotoxic activity that has been known for many years, also have a tumor promoting activity.

32P-postlabelling analysis of DNA adducts in white blood cells of humans exposed to residential wood combustion particulate matter.

Residential wood combustion (RWC) in open fireplaces poses a possible health risk because of the emission into the indoor air of mutagenic and carcinogenic compounds. In the present report it was investigated whether this emission leads to enhanced levels of DNA adducts in white blood cells (WBC) of exposed subjects. Under conditions that most likely reflect the Dutch pattern of use of open fireplaces, RWC increased both indoor air mutagenicity and levels of benzo(a)pyrene (B(a)P) and pyrene. The indirect mutagenicity showed a stronger increase than the direct mutagenicity. The increase in indirect mutagenicity was not directly correlated with the increase in the levels of B(a)P and pyrene. 32P-postlabelling analysis of DNA adducts following nuclease P1 enrichment or butanol extraction revealed low adduct levels. No combustion-related increase in the amount of adducts was observed. Possible explanations for the lack of correlation between air monitoring data and WBC DNA adduct levels are discussed.

Effects on thyroid hormone metabolism and depletion of lung vitamin A in rats by airborne particulate matter.

Thyroxine (T4) and vitamin A are important regulators of normal epithelial differentiation and proliferation and might act in the promotion phase of carcinogenesis. Thyroid hormone and vitamin A metabolism are linked by a common plasma carrier protein, transthyretin (TTR). Polychlorinated biphenyls (PCBs) and related organochlorine compounds deplete vitamin A and thyroxine by interaction with TTR and alteration of their metabolism in hepatic and other organs. In the present report an outdoor airborne particulate matter (APM) extract was tested for both interaction with thyroid hormone and vitamin A metabolism, in order to address the question of whether APM has the potency to deplete vitamin A and thyroid hormones. Furthermore, studies were performed to characterize compounds present in APM that interact with TTR. A third aim was to compare the interaction of APM extracts with TTR and thyroxine-binding globulin (TBG), the major carrier protein for thyroxine in humans. Results showed that a single treatment of rats with an outdoor APM extract depleted plasma thyroxine and triiodothyronine levels and increased plasma retinol levels gradually over the time period studied, while liver retinol, lung retinol, and retinyl palmitate levels were depleted by 30-50%. As outdoor APM was able to inhibit T4-TTR binding in vitro, this suggests that the reduction in thyroxine levels in vivo is caused by the same phenomenon. Experiments showed that the neutral fraction of the APM extract accounted for most of the inhibitory activity on T4-TTR binding. Polycyclic aromatic hydrocarbons and nitrated derivatives are not likely to be responsible for the activity of the neutral fraction, because several representatives of these compounds showed no or very little interaction with TTR. Pentachlorophenol, a compound with known inhibitory activity on T4-TTR binding, was detected in the organic acid fraction of both a cigarette smoke sample and an outdoor APM sample. Finally, it was shown that several indoor and outdoor APM extracts only interact with TTR, but not with TBG. As APM has the potency to deplete lung vitamin A in vivo and vitamin A might have a protective effect in the process of lung carcinogenesis, APM might increase the susceptibility for the development of lung cancer.

Inhibition of binding of thyroxin to transthyretin by outdoor and indoor airborne particulate matter and effects on thyroid hormone and vitamin A metabolism in rats.

Previous studies have indicated that chemicals, e.g., hydroxylated polychlorinated biphenyls (PCBs) decrease plasma thyroxin levels through interaction with transthyretin. As a consequence, plasma vitamin A and thyroxin are depleted. Both thyroxin and vitamin A are important regulators of normal epithelial differentiation and proliferation and might act in the promotion phase of carcinogenesis. In the present report, extracts of indoor and outdoor airborne particulate matter (APM), originating from different pollution sources, were tested for a possible interaction in vitro and in vivo with thyroxin and vitamin A. Results indicated that all APM extracts significantly interfered with thyroxin binding to transthyretin. In all cases, the more polluted samples inhibited binding more than the corresponding control samples. Exposure of rats to a cigarette smoke extract induced clear changes in plasma thyroxin and triiodothyronin hormone levels. Triiodothyronin levels were reduced most. Effects on plasma vitamin A levels were also found, but these were less clear. In addition a decrease in lung vitamin A levels was found, but this decrease was not statistically significant. Exposure of rats to an outdoor APM extract induced significant changes in plasma triiodothyronin levels. Effects on thyroxin levels were not significant, although the same trend was seen as for the cigarette smoke APM extract. No changes in plasma or liver vitamin A concentrations were induced by the outdoor APM extract. Lung vitamin A levels were decreased, but again this decrease was not statistically significant. Taken together, the present report shows that APM extracts have the potency to interfere with thyroid hormone metabolism both in vitro and in vivo and probably with vitamin A metabolism as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of gap-junctional intercellular communication by TPA and airborne particulate matter in primary cultures of rat alveolar type II cells.

Alveolar type II cells were isolated from the lungs of female Wistar rats and were used for studies on inhibition of gap junction mediated intercellular communication (IC). Cells were incubated with 12-O-tetradecanoylphorbol-13-acetate (TPA) or extracts of airborne particulate matter (APM) and subsequently microinjected with the fluorescent dye Lucifer Yellow after which the number of fluorescent (i.e. communicating) cells was determined. Cells exposed to solvent (DMSO), showed an extensive dye coupling. Exposure of cells to TPA or extracts of APM derived from different pollution sources resulted in a strong inhibition of IC. These results show that primary cultures of rat alveolar type II cells can serve pre-eminently as a model in dye-coupling experiments. It further can be concluded that extracts of APM, in addition to the genotoxic activity that has been known for many years, also may have a tumor-promoting potency.

Inhibition of intercellular communication by airborne particulate matter.

To investigate the inhibition of gap junction mediated intercellular communication (IC) by extracts of airborne particulate matter (APM), V79 cells were incubated with extracts of APM and subsequently microinjected with the fluorescent dye Lucifer Yellow, after which the number of fluorescent (= communicating) cells was determined. To compare inhibitory effects on IC with mutagenicity, APM was also tested in the Salmonella microsome assay. Six different extracts were tested, two outdoor extracts representing a heavily polluted and a relatively clean sample, and four indoor extracts, taken either in livingrooms with or without wood combustion in an open fire place, or in a room with or without cigarette smoking. Non-cytotoxic doses of outdoor and indoor APM inhibited IC in V79 cells in a dose- and time-dependent manner. Mutagenicity data and IC data were correlated. These results suggest that APM has tumor promoter activity in addition to mutagenic activity.

Genotoxicity of benzo[a]pyrene, 2-nitrofluorene and airborne particulates in the DNA-repair host-mediated assay.

The genotoxic activity of benzo[a]pyrene (BAP), 2-nitrofluorene (NF) and airborne particulate matter was evaluated in the DNA-repair host-mediated assay after intraperitoneal or intratracheal administration. Dimethylnitrosamine (DMNA), used as a positive control, showed a genotoxic effect after both intraperitoneal and intratracheal administration, the strongest effect being found in liver, followed by lungs and kidneys, whereas a weak effect was observed in the spleen. In general no difference in genotoxicity was found between the 2 administration routes used. For BAP, although clearly positive in vitro, a moderate dose-dependent effect was found only in the liver after intraperitoneal administration. NF, which was positive in vitro both with and without a metabolizing system, produced no genotoxic effect in any of the organs tested after intraperitoneal administration. Extracts of airborne particulate matter which were genotoxic in vitro failed to cause a genotoxic effect in vivo by either route of administration. Possible explanations for the differences between the data obtained in vitro and in vivo are discussed.