Occupational Exposure of Plastics Workers to Diisononyl Phthalate (DiNP) and Di(2-propylheptyl) Phthalate (DPHP) in Finland.

The aim of this study was to assess occupational exposure to diisononyl phthalate (DiNP) and di(2-propylheptyl) phthalate (DPHP] in Finland. Four companies took part in the research project: A cable factory, a plastic producing company, a producer of coated textiles, and a tarpaulin producer. The cable factory used DPHP (and occasionally also diisodecyl phthalate, DiDP), the plastic producing company used both DPHP and DiNP, and the latter two companies used DiNP in their production. Exposure was assessed by measuring phthalate metabolites in urine samples (biomonitoring) and by performing air measurements. Low-level occupational exposure to DiNP was observed in the company that produced coated textiles-out of eight workers, one extruder operator was exposed to DiNP at levels exceeding the non-occupationally exposed population background levels. Some workers in the cable factory and the plastics producing company were occupationally exposed to DPHP. Air levels of phthalates were generally low, mostly below the limit of quantification. All phthalate metabolite concentrations were, however, well below the calculated biomonitoring equivalents, which suggests that the health risks related to the exposure are low.

Environmental and occupational exposure to resorcinol in Finland.

Resorcinol is a suspected endocrine disruptor that affects thyroid function by inhibiting thyroxin peroxidase. It may also have an impact on iodine uptake. Resorcinol has various uses; for example in the manufacture of rubber products and in wood adhesives, flame retardants, UV stabilizers, and dyes. It is also used in personal care products such as hair colorants, anti-acne preparations, and peels. The aim of this study was to assess both environmental background exposure and occupational exposure to resorcinol in Finland. We investigated occupational exposure in hairdresser work and in the manufacture of tyres, adhesive resins and glue-laminated timber by biomonitoring total resorcinol concentration in urine samples. The biomonitoring results were compared to the urinary levels of occupationally non-exposed volunteers, and to the biomonitoring equivalent (BE), which we estimated on the basis of the EFSA's acceptable daily intake (ADI) value for resorcinol. Almost all the urine samples (99%) of the non-occupationally exposed volunteers contained measurable amounts of resorcinol. The urinary resorcinol data were rather scattered, and the resorcinol concentrations among women (GM 84 µg/l, 95th percentile 2072 µg/l) were clearly higher than the respective concentrations among men (GM 35 µg/l, 95th percentile 587 µg/l). The reason for this difference remains unclear. Although the two highest results exceeded the BE of 4 mg/l calculated on the basis of the EFSA's ADI, the 95th percentile of the occupationally non-exposed volunteers' results remained well below the BE among both males and females. According to the results, hairdressers' exposure to resorcinol was at the same level as that of the reference population of occupationally non-exposed volunteers. All hairdresser's values remained below the BE for resorcinol. The urinary resorcinol levels of the industrial workers were also at the same level as those of the reference population. We observed slight increases in the post-shift and evening samples of those working in the manufacture of tyres and adhesive resins. The results of some workers in the tyre manufacturing company exceeded the 95th percentile of non-occupationally exposed males, which was used as a biological guidance value for occupational exposure. Moreover, in this case exposure was below the health-based biomonitoring equivalents. All the air samples collected in the companies contained very low resorcinol concentrations. It should be noted that the sample sizes for the male controls and industrial groups were small.

Co-exposure with fullerene may strengthen health effects of organic industrial chemicals.

In vitro toxicological studies together with atomistic molecular dynamics simulations show that occupational co-exposure with C60 fullerene may strengthen the health effects of organic industrial chemicals. The chemicals studied are acetophenone, benzaldehyde, benzyl alcohol, m-cresol, and toluene which can be used with fullerene as reagents or solvents in industrial processes. Potential co-exposure scenarios include a fullerene dust and organic chemical vapor, or a fullerene solution aerosolized in workplace air. Unfiltered and filtered mixtures of C60 and organic chemicals represent different co-exposure scenarios in in vitro studies where acute cytotoxicity and immunotoxicity of C60 and organic chemicals are tested together and alone by using human THP-1-derived macrophages. Statistically significant co-effects are observed for an unfiltered mixture of benzaldehyde and C60 that is more cytotoxic than benzaldehyde alone, and for a filtered mixture of m-cresol and C60 that is slightly less cytotoxic than m-cresol. Hydrophobicity of chemicals correlates with co-effects when secretion of pro-inflammatory cytokines IL-1ß and TNF-α is considered. Complementary atomistic molecular dynamics simulations reveal that C60 co-aggregates with all chemicals in aqueous environment. Stable aggregates have a fullerene-rich core and a chemical-rich surface layer, and while essentially all C60 molecules aggregate together, a portion of organic molecules remains in water.

Exposure to flame retardants in electronics recycling sites.

Waste electrical and electronic equipment (WEEE) contains various hazardous substances such as flame retardants (FRs). Inhalation exposures to many FRs simultaneously among WEEE recycling site workers have been little studied previously. The breathing zone airborne concentrations of five brominated FR compounds tetrabromobisphenol-A (TBBP-A), decabromodiphenylethane (DBDPE), hexabromocyclododecane, 1,2-bis(2,4,6-tribromophenoxy)ethane, hexabromobenzene, and one chlorinated FR (Dechlorane Plus®) were measured at four electronics recycling sites in two consecutive years. In addition, concentrations of polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyls were measured. The three most abundant FRs in personal air samples were PBDEs (comprising mostly of deca-BDE), TBBP-A, and DBDPE, with mean concentrations ranging from 21 to 2320 ng m(-)(3), from 8.7 to 430 ng m(-3), and from 3.5 to 360 ng m(-3), respectively. At two of the sites, the emission control actions (such as improvements in ventilation and its maintenance and changes in cleaning habits) proved successful, the mean levels of FRs in personal samples being 10-68 and 14-79% of those from the previous year or alternatively below the limit of quantification. At the two remaining sites, the reductions in FR exposures were less consistent. The concentrations reported may pose a health hazard to the workers, although evaluation of the association between FR exposure and adverse health effects is hampered by lacking occupational exposure limits. Therefore, the exposures should be minimized by adequate control measures and maintaining good occupational hygiene practice.

Micronuclei, hemoglobin adducts and respiratory tract irritation in mice after inhalation of toluene diisocyanate (TDI) and 4,4'-methylenediphenyl diisocyanate (MDI).

Toluene diisocyanate (TDI) and 4,4'-methylenediphenyl diisocyanate (MDI), used in the production of polyurethane foam, are well known for their irritating and sensitizing properties. Contradictory results have been obtained on their genotoxicity. We investigated the genotoxicity and protein binding of inhaled TDI and MDI in mice by examining micronucleated polychromatic erythrocytes (PCEs) in bone marrow and peripheral blood and TDI- and MDI-derived adducts in hemoglobin. Male C57Bl/6J mice (8 per group) were exposed head-only to TDI vapour (mean concentrations 1.1, 1.5, and 2.4mg/m(3); the mixture of isomers contained, on the average, 63% 2,4-TDI and 37% 2,6-TDI) or MDI aerosol (mean concentrations 10.7, 20.9 and 23.3mg/m(3)), during 1h/day for 5 consecutive days. Bone marrow and peripheral blood were collected 24h after the last exposure. Inhalation of TDI caused sensory irritation (SI) in the upper respiratory tract, and cumulative effects were observed at the highest exposure level. Inhalation of MDI produced SI and airflow limitation, and influx of inflammatory cells into the lungs. Hemoglobin adducts detected in the exposed mice resulted from direct binding to globin of 2,4- and 2,6-TDI and MDI, and dose-dependent increases were observed especially for 2,4-TDI-derived adducts. Adducts originating from the diamines of TDI (toluene diamine) or MDI (methylene dianiline) were not observed. No significant increase in the frequency of micronucleated PCEs was detected in the bone marrow or peripheral blood of the mice exposed to TDI or MDI. The ratio of PCEs and normochromatic erythrocytes (NCEs) was reduced at the highest concentration of MDI, and a slight reduction of the PCE/NCE ratio, dependent on cumulative inhaled dose, was also seen with TDI. Our results indicate that inhalation of TDI or MDI (1h/day for 5 days), at levels that induce toxic effects and formation of TDI- or MDI-specific adducts in hemoglobin, does not have detectable genotoxic effects in mice, as studied with the micronucleus assay.

Protein adducts as biomarkers of exposure to aromatic diisocyanates in workers manufacturing polyurethane (PUR) foam.

This work was undertaken to investigate the usefulness of diisocyanate-related protein adducts in blood samples as biomarkers of occupational exposure to toluene diisocyanate (TDI; 2,4- and 2,6-isomers) and 4,4'-methylenediphenyl diisocyanate (MDI). Quantification of adducts as toluene diamines (TDAs) and methylenedianiline (MDA) was performed on perfluoroacylated derivatives by gas chromatography-mass spectrometry (GC-MS/MS) in negative chemical ionisation mode. TDI-derived adducts were found in 77% of plasma and in 59% of globin samples from exposed workers manufacturing flexible polyurethane foam. The plasma levels ranged from 0.003 to 0.58 nmol mL(-1) and those in globin from 0.012 to 0.33 nmol g(-1). The 2,6-isomer amounted to about two-thirds of the sum concentration of TDA isomers. MDI-derived adducts were detected in 3.5% of plasma and in 7% of globin samples from exposed workers manufacturing rigid polyurethane foam. A good correlation was found between the sum of TDA isomers in urine and that in plasma. The relationship between globin adducts and urinary metabolites was ambiguous. Monitoring TDI-derived TDA in plasma thus appears to be an appropriate method for assessing occupational exposure. Contrary to TDI exposure, adducts in plasma or globin were not useful in assessing workers' exposure to MDI. An important outcome of the study was that no amine-related adducts were detected in globin samples from TDI- or MDI-exposed workers, alleviating concerns that TDI or MDI might pose a carcinogenic hazard. Further studies are nevertheless required to judge whether diisocyanates per se could be such a hazard.

Analysis of 8-hydroxy-2'-deoxyguanosine in urine using high-performance liquid chromatography-electrospray tandem mass spectrometry.

8-hydroxy-2'-deoxyguanosine (8-OHdG) is a widely used biomarker of oxidative stress in research related to DNA, protein damage as well as lipid peroxidation. HPLC-MS/MS with electrospray ionization (ESI) and the use of isotopically labelled 8-OHdG as an internal standard allows a simple quantification of 8-OHdG in urine samples. HPLC separation utilized the peak cutting technique and a 1.5 mmx120 mm analytical anion exchange column. Novel method entails only minimal sample handling including the addition of a buffer and an internal standard followed by centrifugation before the samples are ready for analysis. The levels of 8-OHdG in human urine samples (n=246) varied from 0.16 to 16.48 microg/L and the corresponding creatinine-normalized values were ranged from 0.49 to 14.27 microg of 8-OHdG/g creatinine. The correlation between the developed HPLC-MS/MS method and the existing HPLC-EC method was good with an R2 value of 0.8707.

Exposure to methylhexahydrophthalic anhydride (MHHPA) in two workplaces of the electric industry.

Methylhexahydrophthalic anhydride (MHHPA) is a hardener for hot-cured epoxy resins employed as insulators in the electric industry. MHHPA has only been measured as an ingredient with other alicyclic anhydrides, albeit there are also large processes which use only MHHPA. We collected MHHPA vapour in a set of devices: Teflon filter, glass spiral, TenaxTA tube connected consecutively together. Elution was performed with a solvent mixture of methyl-tert-butyl ether (70%), acetonitrile (30%), and acetic anhydride (0.5%). By capillary GC-ECD, the regression was linear (0.9994) in the practical low concentration range of 0.04-1 microg ml(-1) being equal to 0.001-0.035 mg m(-3) in 30 l of air. The exposure was measured in two factories manufacturing electric appliances. The assembled objects were first impregnated with a liquid epoxy/hardener mixture, and then the resin hardened at elevated temperature. In condenser manufacturing, the operators' 8 h exposure ranged from 0.068 to 0.118 mg m(-3), and the short-term exposure was during operation at ovens mean 1.90 mg m(-3). The impregnation of coiled resistors and transfer of them to ovens caused the worst exposures, short-term mean 3.846 mg m(-3) and long-term mean 2.191 mg m(-3). During the 'baking', the ovens were closed and evacuated, but when the hot objects were moved out of the ovens, they continued during chilling to emit MHHPA, mean 0.366 mg m(-3). In the adjacent areas, assembling, control rooms, offices, the exposure was still significant, 0.017-0.043 mg m(3), due to leaks from the high exposure areas. Mechanical general ventilation and local exhausts were functioning. Respirators were available for short supervising of the hot equipment.

Role of amino acid N-methylation in cyclosporins on ring opening and fragmentation mechanisms during collisionally induced dissociation in an ion trap.

The product ion mass spectra (collisionally induced dissociation mass spectra) of 12 different cyclosporins modified at every N-methylated amino acid residue with respect to cyclosporin A were compared and the effect of N-demethylation on ring opening mechanisms was evaluated. The four preferential protonation sites were identified in [MeBmt(1)]-cyclosporins. Three sites represented the N-methylated nitrogens of Sar(3), MeLeu(6) and MeLeu(9), while the remaining one represented the lactone group formed by the intramolecular N,O-acyl shift. Selective N-demethylation resulted either in the deletion of the entire fragment ion series or its substantial attenuation. The structures of three new natural cyclosporins in the study were supported by NMR data.