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.

Cytotoxicity and genotoxicity in vitro and irritation potency in vivo of two red phosphorus-based pyrotechnic smokes.

Two red phosphorus (RP)-based smokes (P60 and RPB), differing from each other mainly in RP content and in type of additive, were evaluated for in vitro cytotoxicity (cell viability by the trypan-blue exclusion method) and genotoxicity (comet assay) by exposing BEAS 2B human bronchial epithelial cells to the smokes in a laboratory-scale chamber for 5 min. The irritation potency of RPB smoke was studied in mice. A hexachloroethane-based smoke (HC/Zn/TNT) was used as a reference in the studies. A 5-min exposure of BEAS 2B cells to P60 smoke (1.1, 2.2 and 4.4 g/m(3), measured as H(3)PO(4)) did not induce any cytotoxic effects, while RPB smoke (1.3, 2.6 and 5.1g/m(3), measured as H(3)PO(4)) caused a mild decrease in cell viability at higher concentrations, without a clear dose-dependent effect. Neither of the RP smokes showed a genotoxic response in the comet assay with BEAS 2B cells, while HC/Zn/TNT was clearly genotoxic (0.9-3.5 g/m(3) as ZnCl(2)). In the mouse bioassay, head-only exposure to RPB smoke (20-450 mg/m(3) for 30 min as a single exposure, or 65-90 and 25-110 mg/m(3) - measured as H(3)PO(4) - for 30 min/day during 5 days) caused a concentration-dependent sensory irritation, which was evident as a decrease in respiratory rate and an increase in time-of-pause after inspiration, in a similar manner as with HC/Zn/TNT smoke. The concentration that caused a 50% decrease in respiratory frequency (RD(max)50) was calculated to be 1140 mg/m(3) for the RPB smoke and 145 mg/m(3) for the HC/Zn/TNT smoke. No pulmonary irritation was observed.

Microbial volatile organic compounds.

Microbial volatile organic compounds (MVOCs) are a variety of compounds formed in the metabolism of fungi and bacteria. Of more than 200 compounds identified as MVOCs in laboratory experiments, none can be regarded as exclusively of microbial origin or as specific for certain microbial species. Thus, the recognition of microbially contaminated areas by MVOC measurements is not successful with current methods. In this review, the basic physical and chemical properties of 96 typical MVOCs have been summarised. Of these, toxicological and exposure data were gathered for the 15 MVOCs most often analysed and reported in buildings with moisture and microbial damage. The most obvious health effect of MVOC exposure is eye and upper-airway irritation. However, in human experimental exposure studies, symptoms of irritation have appeared at MVOC concentrations several orders of magnitude higher than those measured indoors (single MVOC levels in indoor environments have ranged from a few ng/m(3) up to 1 mg/m(3)). This is also supported by dose-dependent sensory-irritation response, as determined by the American Society for Testing and Materials mouse bioassay. On the other hand, the toxicological database is poor even for the 15 examined MVOCs. There may be more potent compounds and other endpoints not yet evaluated.

Respiratory and dermal exposure to organophosphorus flame retardants and tetrabromobisphenol A at five work environments.

Organophosphorus compounds (OPs) and tetrabromobisphenol A (TBBPA) are widely utilized as flame retardants (FRs) in plastics, textiles, rubbers, and building materials. Eight OPs and TBBPA were quantified by GC/MS from air samples collected from a furniture workshop, a circuit board factory, two electronics dismantling facilities, a computer classroom, and offices and social premises. In addition, dermal exposure was assessed with patch and hand wash samples at some workplaces. Triphenyl phosphate, tris(2-chloroethyl) phosphate, and tris(2-chloroisopropyl) phosphate were typical contaminants of the workplaces, whereas TBBPA, tricresyl phosphate, tri-n-butyl phosphate, and tris(2-ethylhexyl) phosphate were rather site-specific. The highest geometric mean of total FRs in the air samples was measured in personal samples atthe electronics dismantling facilities (2.9 and 3.8 microg/m3), whereas the stationary sample results from the other environments ranged between 90 and 720 ng/m3. Stationary samplings underestimated the personal exposure at three out of four work places where comparisons were made. Dermal exposure was shown for the first time at these occupational settings. The geometric mean of totalFR levels in patch samples ranged between 1.5 and 24 ng/cm2 and in hand wash samples between 3.5 and 34 microg/ two hands. The health effects of the measured FR levels remain unknown.

Airborne concentrations of volatile organic compounds, formaldehyde and ammonia in Finnish office buildings with suspected indoor air problems.

A database of indoor air concentrations of volatile organic compounds (VOCs) (n = 528), formaldehyde (n = 76), and ammonia (n = 47) in office environments was analyzed to suggest interpretation guidelines for chemical measurements in office buildings with suspected indoor air problems. Indoor air samples were collected for VOCs from 176 office buildings, 23 offices for formaldehyde, and 14 office buildings for ammonia in 2001-2006. Although the buildings had reported indoor air complaints, a walk-through inspection by indoor air specialists showed no exceptional sources of indoor air pollutants. The measurements of chemical pollutants did not indicate any clear reason for the complaints. The geometric mean concentration of total volatile organic compounds (TVOC) was 88 microg m(-3) in office rooms and 75 microg m(-3) in the open plan offices. The mechanical supply and exhaust ventilation significantly (p < 0.004) decreased the indoor air concentration of TVOC. The highest mean concentration and frequency distributions were determined for the individual VOCs. The most common VOCs found in > or = 84% of the indoor samples include toluene, xylene (p,m), 1-butanol, nonanal, and benzene. According to concentrations, the most abundant VOCs were 2-(2-ethoxyethoxy)ethanol, acetic acid, 1,2-propanediol, and toluene. The geometric mean concentration of formaldehyde and ammonia in the office buildings was 11 microg m(-3) (3-44 microg m(-3) and 14 microg m(-3) (1-49 microg m(-3), respectively. On the basis of statistical analyses, the guideline value indicating a usual concentration of the pollutant in office buildings is 70 microg m(-3) for TVOC, 7 microg m(-3) for most individual VOCs, 10 microg m(-3) for formaldehyde, and 12 microg m(-3) for ammonia. The guidance value suggested for TVOC is 250 microg m(-3), for formaldehyde 15 microg m(-3), and for ammonia 25 microg m(-3). If the guidance value is exceeded, this may indicate the existence of an exceptional source and the need for additional environmental investigations. The levels should not be used for the evaluation of health risks. The guideline values are applicable in a subarctic climate for modern, urban office buildings.

Controlling occupational allergies in the workplace.

OBJECTIVES: In recent years, the prevalence of work-related asthma has increased. Therefore, more attention needs to be paid to occupational allergens and their avoidance and control in workplaces. However, risk assessment of occupational allergen exposure is difficult because the relationship between exposure concentration, sensitization, and symptoms has not been fully established. This paper introduces a systematic and comprehensive approach to assessing and managing allergen risks at workplaces. MATERIALS AND METHODS: This approach relies on the cooperation and active communication during the whole process between management, employees, and health care personnel, with the assistance of experts when needed. In addition to gathering background information, including allergic symptoms, through questionnaires addressed to the management and employees, hazard identification is also processed in the workplace through observations and measurements. The methods generally recommended to reduce allergen exposure are compared with those used in the workplace. The process is to be carefully planned and documented to allow later follow-up and re-evaluation. RESULTS: The multi-faceted approach encompasses several risk assessment techniques, and reveals the prevalence of work-related allergic symptoms. The process effectively focuses on the potential means for controlling allergen exposure. CONCLUSION: Based on this approach, the synopsis on the critical points that require implementation of effective control measures can be presented.

In vivo and in vitro evaluation of the acute toxicity, the genotoxicity, and the irritation potency of two hexachloroethane-based pyrotechnic smokes.

The two hexachloroethane (HC)-based smoke formulations studied consisted of HC/Zn/2,4,6-trinitrotoluene (TNT) and HC/Zn. In the in vitro tests, human bronchial epithelial cells were exposed to the smokes at various concentrations. The responses studied were acute toxicity (viability of cells, trypan blue exclusion method) and genotoxicity (DNA single-strand breaks, COMET assay). The tests were conducted in a laboratory-scale chamber (V = 150 L) and in a container (V = 55 m3). Both smoke formulations appeared to be acutely toxic and genotoxic. For the 0.5- and 1-g burning experiments the responses were more pronounced with HC/Zn/TNT than with HC/Zn smoke. To study the irritation potency of the smokes, the mouse bioassay according to ASTM E 981-84 was applied. The respiratory parameters measured were tidal volume (VT), airflow during expiration at 0.5 VT (VD), time of pause after expiration (TP), time of breaking after inspiration (TB), and the respiratory frequency (BPM; breaths per minute). In the single-exposure experiments, HC/Zn/TNT smoke induced concentration-dependent sensory irritation in mice and the occupational exposure limit (TLV) was estimated to be 4 mg/m3. In the repeated-exposure experiments, HC/Zn/TNT smoke induced sensory irritation at the beginning of the exposure. Pulmonary irritation tended to dominate when the exposures were repeated. With HC/Zn smoke we were unable to generate sufficient high exposure concentrations. In the repeated-exposure experiments, indications of sensory and pulmonary irritation were seen at concentrations used. No evidence of apoptotic cell death was found in caspase-3-like protease activity assay.

Detection of mouse and rat urinary aeroallergens with an improved ELISA.

BACKGROUND: Risk analysis of laboratory animal work presupposes allergen monitoring with sensitive methods. Commercial ELISA kits have recently become available for the detection of mouse (Mus m 1) and rat (Rat n 1) urinary allergen from settled dust samples and air samples with high allergen levels. OBJECTIVE: Our aims were to enhance the sensitivities of the commercial ELISA kits for low aeroallergen levels (less than 1 ng/m(3)) and to test these methods with air samples collected from an animal facility. METHODS: Personal and stationary air samples were collected from an animal facility during various tasks of laboratory animal work and from various premises of the animal facility. RESULTS: The sensitivities of the ELISA assays were improved with a careful choice of analysis parameters and reagents. The detection limits of 0.1 ng/m(3) for Mus m 1 and 0.8 ng/m(3) for Rat n 1 were established. The sensitized assays enabled detection of mouse and rat aeroallergens also from premises in which animals or dirty cages were not present during sampling. CONCLUSION: These sensitive assays will help to perform risk assessment in laboratory animal work. However, there remains a lack of standardized analytic procedures and occupational exposure limits for laboratory animal allergens.

Partial amino acid sequence of a cellulase-like component with IgE-binding properties from Stachybotrys chartarum.

BACKGROUND: The aim of this study was to characterize the amino acid sequence of a selected Stachybotrys chartarum component and to investigate human IgE reactivity against components of S. chartarum and nine other fungal species. METHODS: Human IgE reactivity against S. chartarum and nine other fungal extracts was investigated by the immunoblotting method. For automated amino acid sequencing analyses, the S. chartarum extract was purified by ion exchange chromatography prior to in-gel alkylation and digestion with modified trypsin. RESULTS: Human IgE reactivity was detected against eight components in the S. chartarum extract. Over 80% of the sera from the exposed subjects and less than 50% of the control sera recognized the 33-, 48- and 50-kD S. chartarum components. The human sera detected a 48- to 50-kD component from the extracts of eight fungal species. Nineteen peptide sequences were identified from the 48-kD component of S. chartarum. An analysis of the peptide sequences revealed homology with known fungal glycoside hydrolase enzymes (cellulases). CONCLUSIONS: The data showed human IgE reactivity against several S. chartarum components, including one at 48 kD. On the other hand, the human sera recognized 48- to 50-kD components from seven other fungal species, suggesting shared antigenic components (e.g. enolase) between the fungi. Thus, to our knowledge, this is the first antigen identified from S. chartarum.