Negligible respiratory irritation and inflammation potency of pigmentary TiO2 in mice.

Titanium dioxide (TiO2) is manufactured in millions of tons yearly, and it is used widely as pigment in various applications. Until recently, TiO2 was considered toxicologically harmless and without adverse health effects. In this study, respiratory irritation and inflammation potencies of commercially available pigmentary TiO2 particles (<5 µm, rutile) were studied. Single head-only exposures (30 min) of male Crl:OF1 mice at mass concentrations 6, 11, 21, and 37 mg/m3, and repeated exposures (altogether 16 h, 1 h/day, 4 days/week for 4 weeks) of female BALB/c/Sca mice at mass concentration of 16 mg/m3 to pigmentary TiO2 were conducted. Minor sensory irritation was observed during acute and repeated exposures seen as elongation of the break after the inhalation, which is typical in sensory irritation, and caused by closure of the glottis inhibiting airflow from the lungs after inspiration. No pulmonary irritation, airflow limitation, nasal or pulmonary inflammation was observed. In conclusion, the respiratory irritation and inflammation potencies of the studied pigmentary TiO2 particles seemed to be low and thus can serve as an ideal control exposure agent in short-term studies in mice.

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.

Nanosized TiO2 caused minor airflow limitation in the murine airways.

The use of nanotechnology is increasing exponentially, whereas the possible adverse health effects of engineered nanoparticles (NPs) are so far less known. Standardized mouse bioassay was used to study sensory and pulmonary irritation, airflow limitation, and inflammation potency of nanosized TiO(2). Single exposure (0.5 h) to in situ generated TiO(2) (primary particle size 20 nm; geometric mean diameters of 91, 113, and 130 nm at mass concentrations of 8, 20, and 30 mg/m(3), respectively; crystal phase anatase + brookite (3:1)) caused airflow limitation in the conducting airways at each studied exposure concentration, which was shown as a reduction in expiratory flow, being at the lowest 73% of baseline. The response was not dose dependent. Repeated exposures (altogether 16 h, 1 h/day, 4 days/week for 4 weeks) to TiO(2) at mass concentration of 30 mg/m(3) caused as intense airflow limitation effect as the single exposures, and the extent of the responses stayed about the same along the exposure days. Sensory irritation was fairly minor. Pulmonary irritation was more pronounced during the latter part of the repeated exposures compared to the single exposures and the beginning of the repeated exposures. Sensory and pulmonary irritation were observed also in the control group, and, therefore, reaction by-products (NO(2) and C(3)H(6)) may have contributed to the irritation effects. TiO(2) NPs accumulated mainly in the pulmonary macrophages, and they did not cause nasal or pulmonary inflammation. In conclusion, the irritation and inflammation potencies of studied TiO(2) seemed to be low.

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.

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.

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.

Inhaled silica-coated TiO2 nanoparticles induced airway irritation, airflow limitation and inflammation in mice.

The wide use of nanotechnology is here to stay. However, the knowledge on the health effects of different engineered nanomaterials (ENMs) is lacking. In this study, irritation and inflammation potential of commercially available silica-coated TiO2 ENMs (10 × 40 nm, rutile) were studied. Single exposure (30 min) at mass concentrations 5, 10, 20 and 30 mg/m(3), and repeated exposure (altogether 16 h, 1 h/day, 4 days/week for 4 weeks) at mass concentration of 30 mg/m(3) to silica-coated TiO2 induced first phase of pulmonary irritation (P1), which was seen as rapid, shallow breathing. During repeated exposures, P1 effect was partly evolved into more intense pulmonary irritation. Also sensory irritation was observed at the beginning of both single and repeated exposure periods, and the effect intensified during repeated exposures. Airflow limitation started to develop during repeated exposures. Repeated exposure to silica-coated TiO2 ENMs induced also pulmonary inflammation: inflammatory cells infiltrated in peribronchial and perivascular areas of the lungs, neutrophils were found in BAL fluids, and the number of CD3 and CD4 positive T cells increased significantly. In line with these results, pulmonary mRNA expression of chemokines CXCL1, CXCL5 and CXCL9 was enhanced. Also expression of mRNA levels of proinflammatory cytokines TNF-α and IL-6 was elevated after repeated exposures. Taken together, these results indicated that silica-coated TiO2 ENMs induce pulmonary and sensory irritation after single and repeated exposure, and airflow limitation and pulmonary inflammation after repeated exposure.

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.

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.

Effects of aerosols from nontoxic Stachybotrys chartarum on murine airways.

Acute effects on the upper and lower respiratory tract due to inhalation exposure to Stachybotrys chartarum (Sc) extract were investigated in mice. In addition, the capacity of the Sc exposure to activate immune system and cause inflammation in the respiratory tract was studied. The inhalation of Sc extract aerosols was observed to provoke sensory irritation in the airways of both naive and Sc-immunized mice. In contrast, exposure to aerosolized ovalbumin or phosphate buffered saline did not cause this effect. Exposure to Sc twice a week for 3 wk increased significantly the serum total immunoglobulin E (IgE) levels in BALB/c mice immunized with Sc as well as in nonimmunized mice. A slight presence of inflammatory cells was observed in the alveoli 3 days after the last exposure to Sc. In conclusion, Sc extract has the capacity to provoke sensory irritation in the murine airways and to activate the murine immune system.