Quantification of tire wear particles in road dust based on synthetic/natural rubber ratio using pyrolysis-gas chromatography-mass spectrometry across diverse tire types.

Increase in road traffic leads to increased concentrations of tire-wear particles (TWPs), a prominent source of microplastics from vehicles, in road dust. These particles can re-enter the atmosphere or move into aquatic ecosystems via runoff, impacting the environment. Consequently, accurately assessing and managing TWP levels in road dust is crucial. However, the ISO method (ISO/TS 20593 and 21396) uses a constant ratio of styrene-butadiene rubber (SBR) to natural rubber (NR) for all tires, disregarding the variability in tire composition across different types and brands. Our study found substantial SBR content (15.7 %) in heavyweight truck tires, traditionally believed to be predominantly NR. We evaluated the SBR/NR content in 15 tire types and proposed a method to more accurately evaluate TWP concentrations in road dust from five different locations. Our findings suggest that the conventional ISO method may underestimate the concentrations of TWP due to its reliance on a static ratio of SBR/NR. This study underscores the necessity for a more flexible approach that can adapt to the variability in SBR and NR content across different tire types. By delineating the limitations inherent in current assessment methods, our research contributes to a more adaptable understanding of TWP concentrations in road dust. This advancement prompts the development of a revised methodology that more accurately reflects the diverse compositions of tire rubber in environmental samples.

Association of immunotoxicological indices with lung cancer biomarkers in poultry, grape, and rose farming workers.

Exposure to occupational hazards like dust, pesticides, diesel emission particles, or physical hazards in the agricultural sector is known to cause adverse health effects on farm workers. Our study aimed at addressing the association of immunomodulatory status with plasma levels of lung cancer biomarkers in farming population, attempting to recognition of vulnerable farming group. Blood samples from apparently healthy 51 chicken husbandry, 19 grape orchard, and 21 rose greenhouse workers were subjected to evaluate plasma levels of two representative lung cancer biomarkers, pro-gastrin releasing peptide (Pro-GRP) and cytokeratin fragment 19 (CYFRA 21-1). Peripheral blood mononuclear cells obtained from farmers were used for natural killer (NK) cell phenotyping and cytokines (interferon-gamma, IFN-γ and interleukin-13, IL-13) profiling in the culture supernatant. Compared to the rose greenhouse farmers, the grape orchard and chicken husbandry workers revealed a significantly upregulated plasma Pro-GRP and CYFRA 21-1 level. A low proportion of NK cells was observed among the female grape orchard workers and a lowered IFN- γ:IL-13 ratio was seen in the grape and chicken husbandry workers than the rose workers. Our findings imply that grape orchard and chicken husbandry workers have more disturbed immune homeostasis implicated with augmentation in the levels of lung cancer biomarkers than the rose greenhouse workers.

Rapid estimation of tire-wear particle concentration in road dust using PM10 and traffic data in a ternary plot.

Air pollution, a pressing global issue, is significantly exacerbated by airborne particulate matter (PM), affecting air quality and human health. Urban vehicular activities majorly contribute to PM rise through both exhaust and non-exhaust emissions. Despite strides in managing exhaust emissions, non-exhaust particles, such as tire wear particles (TWP) remain under-addressed. This research proposes a method for estimating TWP concentrations using PM10 data and traffic activity, which could offer a valuable tool for controlling roadside fine particles and TWP. This paper introduces a ternary plotting technique and step-by-step procedure to estimate TWP levels in road dust using only PM10 and traffic data. Traditional analysis of TWP via pyrolysis-gas chromatography-mass spectrometry is complex and time-consuming. Hence, our proposed approach presents an alternate method that leverages readily accessible PM and traffic data, providing critical information for road management interpretation. The triangular plot analysis demonstrated a linear correlation: [log(Traffic) + 2]-[250,000/TWP-13]-0.18PM10. While the resulting correlation may vary based on specific road conditions, the method can be tailored to different regions, offering insights into efficient estimation of TWP concentrations and promoting improved roadside pollution management.

Immunodysregulatory potentials of polyethylene or polytetrafluorethylene microplastics to mice subacutely exposed via intragastric intubation.

Microplastics (MPs) have been recently recognized as posing a risk to human health. The adverse health effects of MP exposure have been recently reported, especially via the oral exposure route. The present study investigated whether subacute (4 week) exposure to polyethylene (PE) or polytetrafluorethylene (PTFE) MPs via gastric intubation caused immunotoxicity. Two different sizes of PE MPs (6.2 or 27.2 µm) and PTFE MPs (6.0 or 30.5 µm) were administered to 6-week-old mice of both sexes at 0 (corn oil vehicle control), 500, 1000, or 2000 mg/kg/day (n = 4/group). No significant differences were observed between groups in the major thymic or splenic immune cell populations, including thymic CD4+, CD8+, CD4+/CD8+ T lymphocytes, and splenic helper T cells, cytotoxic T cells, and B cells. The ratio of interferon-gamma (IFNγ) to interleukin-4 (IL-4) in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo (48 h) was dose-dependently decreased in female mice that received small- and large-size PTFE MPs. The IFNγ/IL-4 ratio was also decreased in the female mice dosed with large-size PE MPs. The serum IgG2a/IgG1 ratio was dose-dependently increased in male and female animals dosed with small-size PE MPs, in female animals dosed with large-size PTFE MPs, and in male animals dosed with small-size PTFE MPs. The present study implies that immune functions could be affected in animals exposed to MPs via gastric intubation. These effects are dependent on MP size, MP dose, MP polymer type, and mouse sex. Further investigations with longer exposure periods could be necessary to more clearly define the immunotoxic effects of MPs. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00172-6.

Polytetrafluorethylene microplastic particles mediated oxidative stress, inflammation, and intracellular signaling pathway alteration in human derived cell lines.

Microplastics (MPs) are now widely distributed across the aerial, terrestrial, and aquatic environments. Thus, exposure to MPs via the oral, inhalation, or dermal routes is inevitable. Polytetrafluoroethylene (PTFE)-MPs is mainly used for manufacturing nonstick cookware, semiconductors, and medical devices; however, their toxicity has been rarely studied. In the present study, six different human cell lines, which are representative of tissues and cells that directly or indirectly come into contact with MPs, were exposed to two different sizes of irregular shape PTFE-MPs (with an average diameter of 6.0 or 31.7 µm). PTFE-MPs-mediated cytotoxicity, oxidative stress, and changes in proinflammatory cytokine production were then evaluated. We found that the PTFE-MPs did not induce cytotoxicity under any of the experimental conditions. However, PTFE-MPs (especially average diameter of 6.0 µm) induced nitric oxide and reactive oxygen species production in all the cell lines tested. Moreover, both sizes of PTFE-MPs increased the secretion of tumor necrosis factor alpha and interleukin-6 from the U937 macrophage cell line and the A549 lung epithelial cell line, respectively. In addition, PTFE-MPs activated the MAPK signaling pathways, especially the ERK pathway, in A549 and U937 cells, and in the THP-1 dendritic cell line. We also found that the expression of the NLRP3 inflammasome was reduced in the U937 and THP-1 cell lines following treatment with the PTFE-MPs sized 31.7 µm average diameter. Furthermore, expression of the apoptosis regulator, BCL2, was markedly increased in the A549 and U937 cell lines. Thus, although PTFE-MPs exert different effects on different cell types, our findings suggest that PTFE-MPs-associated toxicity may be specifically linked to the activation of the ERK pathway, which ultimately induces oxidative stress and inflammation.

Rapid generation of aged tire-wear particles using dry-, wet-, and cryo-milling for ecotoxicity testing.

Strict environmental laws have been enacted to regulate the emission of exhaust particulate matter (PM), which is one of the most hazardous pollutants that reduce air quality and pose a serious risk to the human health. In addition, non-exhaust PM, such as road wear, tire wear, and brake wear debris, is a significant source of airborne pollutants. Road dust less than 100 µm in size may include tire wear particles (TWPs), which are broken down into finer particles with sizes on the order of tens of micrometers because of weathering. TWPs can be transported to water bodies via runoff, potentially contaminating water systems and negatively affecting aquatic ecosystems. Therefore, ecotoxicity tests using reference TWPs are required to investigate the impact of TWPs on the human health and environment. In this study, aged TWPs were produced using dry-, wet-, and cryo-milling methods, and the dispersion stability of TWPs in dechlorinated water was evaluated. Aged TWPs prepared by dry- and wet-milling had an average particle size of 20 µm, whereas pristine TWPs had an irregular shape and average particle size of 100 µm. The capacity of the ball-milling cylinder and excessively long 28-d generation time constrain the amount of aged TWPs that can be produced through conventional milling. In contrast, cryo-milling reduces the particle size of TWPs at the rate of -275.0 µm/d, which is nine times higher than that upon dry- and wet-milling. Dispersed cryo-milled TWPs had a hydrodiameter of 2.02 µm and were more stable in the aqueous phase in relation to the other aged TWPs. The results of this study suggest that cryo-milled TWPs can be used for aquatic exposure assessments as controls for real-world TWPs.

Overall distribution of tire-wear particles, nano­carbon black, and heavy metals in size-fractionated road dust collected from steel industrial complexes.

Tire-wear particles (TWP) from vehicles serves as a non-exhaust emission source. The mass content of metallic species in road dust may increase owing to the traffic of heavy vehicles and industrial activity; consequently, metallic particles are also present in road dust. Herein, road dust collected from steel industrial complexes with high traffic of high-weight vehicles and the composition distribution of five size-fractioned particle sizes were analyzed. Road dust samples were collected from three areas near steelmaking complexes. The mass distribution of TWP, carbon black (CB), bituminous coal, and heavy metals (Fe, Zn, Mn, Pb, Ni, As, Cu, Cd, and Hg) in different size fractions of road dust was quantified by combining four different analytical techniques. In the magnetic separation for <45 µm fraction, 34.4 wt% and 50.9 wt% was removed for steelmaking and steel-related industrial complexes, respectively. As the particle size decreased, the mass content of Fe, Mn, and TWP increased. The enrichment factors of Mn, Zn, and Ni were higher than two, indicating that they were related to industrial activities in steel complexes. The maximum concentrations of TWP and CB originating from the vehicle varied depending on the region and particle size range: TWP 2.066 wt% at 45-75 µm (industrial complex) and CB 5.559 wt% at 75-160 µm (steel complex). Coal was only found in the steel complex. Finally, to reduce the exposure of the finest particles to road dust, three methods were suggested. Magnetic fraction must be removed from road dust using magnetic separation; the fly dust of coal during transportation must be suppressed, and covers must be used in coal yards; the mass contents of TWP and CB in road dust should be removed by vacuum cleaning instead of water flushing.

Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles.

Copper oxide nanoparticles (CuO NPs) were intratracheally instilled into lungs at concentrations of 0, 0.15, and 1.5 mg/kg bodyweight to 7-week-old Sprague-Dawley rats. The cytotoxicity, immunotoxicity, and oxidative stress were evaluated, followed by proteomic analysis of bronchoalveolar lavage fluid (BALF) and lungs of rats. The CuO NPs-exposed groups revealed dose-dependent increases in total cells, polymorphonuclear leukocytes, lactate dyhydrogenase, and total protein levels in BALF. Inflammatory cytokines, including macrophage inflammatory protein-2 and tumor necrosis factor-α, were increased in the CuO NPs-treated groups. The expression levels of catalase, glutathione peroxidase-1, and peroxiredoxin-2 were downregulated, whereas that of superoxide dismutase-2 was upregulated in the CuO NPs-exposed groups. Five heat shock proteins were downregulated in rats exposed to high concentrations of CuO NPs. In proteomic analysis, 17 proteins were upregulated or downregulated, and 6 proteins were validated via Western blot analysis. Significant upregulation of 3-hydroxy-3-methylglutaryl-CoA synthase and fidgetin-like 1 and downregulation of annexin II, HSP 47 and proteasome α1 occurred in the CuO NPs exposed groups. Taken together, this study provides additional insight into pulmonary cytotoxicity and immunotoxicity as well as oxidative stress in rats exposed to CuO NPs. Proteomic analysis revealed potential toxicological biomarkers of CuO NPs, which also reveals the toxicity mechanisms of CuO NPs.

Low-Level Environmental Mercury Exposure and Thyroid Cancer Risk Among Residents Living Near National Industrial Complexes in South Korea: A Population-Based Cohort Study.

Background: Previous studies suggested that mercury may be linked to thyroid cancer due to its bioaccumulation in the thyroid gland, but no studies have evaluated the association between mercury exposure and thyroid cancer risk. We examined the relationship between mercury exposure and thyroid cancer risk, with the potential modification of hematological parameters. Methods: We performed a secondary analysis of a prospective cohort study among residents living near industrial complexes in South Korea (recruited from 2003 to 2011). Incident thyroid cancer cases (C73, ICD-10 code) were identified from the National Cancer Registry and Statistics Korea. Urinary mercury concentrations were measured using thermal decomposition amalgamation atomic absorption spectrometry (TDA-AAS). Cox proportional hazards regression models (adjusted for age, sex, educational level, smoking status, and employment) were used to estimate the hazard ratio (HR) and confidence interval [CI] between mercury exposure and the incidence of thyroid cancer. Results: We documented 69 cases of thyroid cancer in a total of 5213 participants during follow-up (median 8.7 years). The geometric mean of urinary mercury concentration was 1.8 µg/L for thyroid cancer cases and 1.2 µg/L for noncases (p for difference = 0.001). After adjusting for potential confounders, those in the highest tertile of urinary mercury levels had a twofold higher risk of thyroid cancer (HR = 1.97 [CI 1.03 - 3.80] in the highest tertile vs. the lowest tertile, p for trend = 0.043). This association was stronger for those with lower mean corpuscular volume and mean corpuscular hemoglobin status. Conclusions: Urinary mercury concentration was positively associated with the risk of thyroid cancer among residents living near national industrial complexes, and this association was influenced by red blood cell indices status. These results provide some evidence suggesting the adverse effects of environmental metal pollution in the development of thyroid cancer.

Quantitative analysis of the concentration of nano­carbon black originating from tire-wear particles in the road dust.

Exhaust and non-exhaust particulate matter (PM) is regarded as the most significant airborne during driving. Among the source of non-exhaust PM, the tire-wear particles (TWP) can be quantified using pyrolysis-gas chromatography/mass spectrometry (Py-GC-MS). TWPs are fragmented by continuous weathering once exposed to the road. Approximately 5 wt% of carbon black (CB) bound in the rubber matrix of TWPs tends to detach from it, and thus some portion of free-bound CB could be co-existed in the road dust. Although there are existing methods for analyzing pure CB and TWPs, only few analysis techniques on the amount of free-bound CB in contaminant samples have been discovered. Herein, we propose a method for quantifying the total and free-bound CB in road dust using a combination of four analytical tools: a semi-continuous carbon analyzer, element analyzer, thermogravimetric analyzer, and Py-GC-MS. This study is the first attempt in quantifying the concentration of nano-CB derived from TWPs in road dust. The proposed methodology was applied to the samples collected from five open sites, three closed sites, and four types of air conditioner (AC) filters in passenger vehicles. Compared to the samples obtained in open sites, the road dust in the closed sites exhibited 21.5 times higher TWP content (59,747 mg/kg) and 5.1 times higher free-bound CB content (14,632 mg/kg). In addition, unintentional driver respiratory exposure to PM fixed in the vehicle filters was discovered owing to the increase in CB and TWP contents in aged AC filters.

Estimation of the concentration of nano-carbon black in tire-wear particles using emission factors of PM10, PM2.5, and black carbon.

Particulate matter (PM) from automobile exhaust has drastic effects on human health. The enforcement of environmental laws has controlled vehicle emissions and reduced the total PM. However, another significant source of PM is debris from tire wear, break wear, and road wear. In particular, tire-wear particles (TWPs) are further fragmented into nanoparticles, similar to the PMx or black carbon (BC) sources. As approximately 30 wt% of carbon black (CB) is used as filler in tires, TWPs can fragment into free-bound nano-CB. This study evaluates the emission factors of BC from the ternary plots of PMx and BC to estimate the concentration of nano-CB in TWPs. Based on the emission factors of BC for TWP, approximately 500 monitoring data points were acquired at four different sites. Semi-closed sites in a field measurement test have 2.9-4.0 times larger BC concentration than open sites. The mass concentration of nano-CB evaluated with the BC data and emission factors at the open sites is 22.47-23.96 ng/m3, whereas that at the semi-closed sites is 66.32-90.33 ng/m3. Transmission electron microscopy analysis with scanning mobility particle sizer and selected-area electron diffraction reveals grape-like aggregated nanoparticles, which is considered as CB. To compare the effect of the washing out of airborne particulates by rain, further analysis is conducted on the interior and exterior of the tunnel on a rainy day. While the concentration of PMs was effectively reduced by rainfall, the amount of BC and CB in the interior of a tunnel was not changed. Namely, even under rainfall, nano-CB still exists in the tunnels and thus free-bound CB and nanoparticles released from TWP will be effected on the human health.

Toluene concentrations in the blood and risk of thyroid cancer among residents living near national industrial complexes in South Korea: A population-based cohort study.

BACKGROUND: Toluene is classified as a possible carcinogen, but its role on thyroid cancer is not well established. Vehicle emissions are one of the largest contributed sources of toluene, but no studies evaluating the influence of living near a road on the association between toluene and the incidence of thyroid cancer have been reported. Therefore, we examined potential associations between blood toluene concentrations and incidence risk of thyroid cancer, and an effect modification of living near a road. METHODS: We conducted a prospective cohort study using data from South Korean "Monitoring Project for Exposure to Environmental Pollutants and Health Effects among Residents Living near Industrial Complexes" survey. Study participants living near national industrial complexes were recruited from January 2003 to 2011. Incidence and mortality cases of thyroid cancer (C73, ICD-10 code) were identified using the National Cancer Registry and Statistics Korea, respectively. Blood toluene concentrations were measured using gas chromatography mass spectrometry. We used Cox proportional hazards regression models to estimate the hazard ratios (HR) and the 95% confidence interval (CI) between blood toluene concentrations and thyroid cancer risk. RESULTS: During the follow-up (median 8.6 years), 33 cases of thyroid cancer were diagnosed. The geometric mean of the toluene concentration in the blood was 0.56 µg/L for cases and 0.29 µg/L for non-cases. After adjusting for potential confounders, a positive association between blood toluene concentrations and thyroid cancer was found (HR = 2.77, 95% CI = 1.00-7.65 in the highest tertile vs. the lowest tertile, p for trend = 0.044). This positive association was stronger in people living near a road (≤50 m). CONCLUSIONS: Blood toluene concentrations may be positively associated with the incidence risk of thyroid cancer. Moreover, this association may be stronger among people living near a road.

Environmental exposure to cadmium and risk of thyroid cancer from national industrial complex areas: A population-based cohort study.

BACKGROUND: Cadmium is known to act as a thyroid disruptor and carcinogen in humans. Recent evidence suggests that cadmium may play a role as a thyroid carcinogen due to its endocrine-disrupting activity, but this characterization remains unclear. OBJECTIVE: We investigated the association between urinary cadmium and primary thyroid cancer, and the modifying effect of diabetes on this association. METHODS: We included 5406 participants over 19 years old with measured urinary cadmium from samples collected at eight National Industrial Complex areas from 2003 to 2011. Among 5406 participants, 68 cases were diagnosed with thyroid cancer between enrollment and the end of follow-up (December 31, 2016). Incidence rate ratios for thyroid cancer were estimated using random-effects Cox proportional hazards models with follow-up time as the time scale. In addition, we conducted a stratified analysis by diabetes status. RESULTS: Compared with the lowest tertile, the middle and highest tertiles had higher risks of thyroid cancer, respectively (HRmiddle vs. lowest = 1.90, 95% CI = 0.93 to 3.91; HRhighest vs. lowest = 2.28, 95% CI = 1.09 to 4.78), with a significant dose-response relationship (P for trend = 0.03). There was no linear association between cadmium level and risk of thyroid cancer. Higher cadmium levels increased thyroid cancer risk in participants without diabetes (HRmiddle vs. lowest = 2.35, 95% CI = 1.05 to 5.24; HRhighest vs. lowest = 2.70, 95% CI = 1.18 to 6.19); although, an association between cadmium levels and thyroid cancer risk in participants with diabetes was not found. CONCLUSION: Low-level exposure to cadmium is associated with thyroid cancer risk. Our results provide the evidence to limit exposure to cadmium for cancer prevention in the general population. Further studies are needed to investigate the consequence of diabetes and antidiabetic drugs between cadmium and thyroid cancer.

Concentration- and Time-Dependent Effects of Benzalkonium Chloride in Human Lung Epithelial Cells: Necrosis, Apoptosis, or Epithelial Mesenchymal Transition.

Benzalkonium chloride (BAC), an antimicrobial agent in inhalable medications and household sprays, has been reported to be toxic to pulmonary organs. Although cell membrane damage has been considered as the main cytotoxic mechanism of BAC, its concentration- and time-dependent cellular effects on lung epithelium have not been fully understood. In the present study, human lung epithelial (H358) cells were exposed to 0.2-40 µg/mL of BAC for 30 min or 21 days. Cell membranes were rapidly disrupted by 30 min exposure, but 24 h incubation of BAC (4-40 µg/mL) predominantly caused apoptosis rather than necrosis. BAC (2-4 µg/mL) induced mitochondrial depolarization, which may be associated with increased expression of pro-apoptotic proteins (caspase-3, PARP, Bax, p53, and p21), and decreased levels of the anti-apoptotic protein Bcl-2. The protein expression levels of IRE1α, BiP, CHOP, and p-JNK were also elevated by BAC (2-4 µg/mL) suggesting the possible involvement of endoplasmic reticulum stress in inducing apoptosis. Long-term (7-21 days) incubation with BAC (0.2-0.6 µg/mL) did not affect cell viability but led to epithelial-mesenchymal transition (EMT) as shown by the decrease of E-cadherin and the increase of N-cadherin, fibronectin, and vimentin, caused by the upregulation of EMT transcription factors, such as Snail, Slug, Twist1, Zeb1, and Zeb2. Therefore, we conclude that apoptosis could be an important mechanism of acute BAC cytotoxicity in lung epithelial cells, and chronic exposure to BAC even at sub-lethal doses can promote pulmonary EMT.

Inhalation toxicity of benzalkonium chloride and triethylene glycol mixture in rats.

Benzalkonium chloride (BAC), a disinfectant, and triethylene glycol (TEG), an organic solvent/sanitizer, are frequently combined in commercially available household sprays. To assess the respiratory effect of this combination, Sprague-Dawley rats were exposed to an aerosol containing BAC (0.5%, w/v) and TEG (10%, w/v) for up to 2 weeks in a whole-body inhalation chamber. BAC (4.1-4.5 mg/m3, sprayed from 0.5% solution) promoted pulmonary cell damage and inflammation as depicted by the increase in total protein, lactate dehydrogenase, polymorphonuclear leukocytes, and macrophage inflammatory protein-2 in the bronchoalveolar lavage fluid, whereas TEG (85.3-94.5 mg/m3, sprayed from 10% solution) did not affect the lung. Rats exposed to the BAC/TEG mixture for 2 weeks showed severe respiratory symptoms (sneezing, wheezing, breath shortness, and chest tightness), but no lung damage or inflammation was observed. However, significant ulceration and degenerative necrosis were observed in the nasal cavities of rats repeatedly exposed to the BAC/TEG mixture. The mass median aerodynamic diameters of the aqueous, BAC, TEG and BAC/TEG aerosols were 1.24, 1.27, 3.11 and 3.24 µm, respectively, indicating that TEG-containing aerosols have larger particles than those of the aqueous and BAC alone aerosols. These results suggest that the toxic effects of BAC and BAC/TEG aerosols on the different respiratory organs may be associated with the difference in particle diameter, since particle size is important in determining the deposition site of inhaled materials.

Evaluation of pulmonary toxicity of benzalkonium chloride and triethylene glycol mixtures using in vitro and in vivo systems.

Benzalkonium chloride (BAC) is a widely used disinfectant/preservative, and respiratory exposure to this compound has been reported to be highly toxic. Spray-form household products have been known to contain BAC together with triethylene glycol (TEG) in their solutions. The purpose of this study was to estimate the toxicity of BAC and TEG mixtures to pulmonary organs using in vitro and in vivo experiments. Human alveolar epithelial (A549) cells incubated with BAC (1-10 µg/mL) for 24 hours showed significant cytotoxicity, while TEG (up to 1000 µg/mL) did not affect cell viability. However, TEG in combination with BAC aggravated cell damage and inhibited colony formation as compared to BAC alone. TEG also exacerbated BAC-promoted production of reactive oxygen species (ROS) and reduction of glutathione (GSH) level in A549 cells. However, pretreatment of the cells with N-acetylcysteine (NAC) alleviated the cytotoxicity, indicating oxidative stress could be a mechanism of the toxicity. Quantification of intracellular BAC by LC/MS/MS showed that cellular distribution/absorption of BAC was enhanced in A549 cells when it was exposed together with TEG. Intratracheal instillation of BAC (400 µg/kg) in rats was toxic to the pulmonary tissues while that of TEG (up to 1000 µg/kg) did not show any harmful effect. A combination of nontoxic doses of BAC (200 µg/kg) and TEG (1000 µg/kg) promoted significant lung injury in rats, as shown by increased protein content and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluids (BALF). Moreover, BAC/TEG mixture recruited inflammatory cells, polymorphonuclear leukocytes (PMNs), in terminal bronchioles and elevated cytokine levels, tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in BALF. These results suggest that TEG can potentiate BAC-induced pulmonary toxicity and inflammation, and thus respiratory exposure to the air mist from spray-form products containing this chemical combination is potentially harmful to humans.

Accumulation of Microcystin (LR, RR and YR) in Three Freshwater Bivalves in Microcystis aeruginosa Bloom Using Dual Isotope Tracer.

Abstract: Stable isotope tracers were first applied to evaluate the Microcystis cell assimilation efficiency of Sinanodonta bivalves, since the past identification method has been limited to tracking the changes of each chl-a, clearity, and nutrient. The toxicity profile and accumulation of MC-LR, -RR and -YR in different organs (foot and digestive organs) from the three filter-feeders (Sinanodonta woodina, Sinanodonta arcaeformis, and Unio douglasiae) were assessed under the condition of toxigenic cyanobacteria (Microcystis aeruginosa) blooms through an in situ pond experiment using 13C and 15N dual isotope tracers. Chl-a concentration in the manipulated pond was dramatically decreased after the beginning of the second day, ranging from 217.5 to 15.6 µg·L-1. The highest amount of MCs was incorporated into muscle and gland tissues in U. douglasiae during the study period, at nearly 2 or 3 times higher than in S.woodiana and S. arcaeformis. In addition, the incorporated 13C and 15N atom % in the U. douglasiae bivalve showed lower values than in other bivalves. The results demonstrate that U. douglasiae has less capacity to assimilate toxic cyanobacteria derived from diet. However, the incorporated 13C and 15N atom % of S. arcaeformis showed a larger feeding capacity than U. douglasiae and S. wodiana. Our results therefore also indicate that S. arcaeformis can eliminate the toxin more rapidly than U. douglasiae, having a larger detoxification capacity.

Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats.

Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20 mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20 mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20 mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5 mg/kg in dams and no observed adverse effect level was suggested to be 10 mg/kg in fetal developmental toxicity.

Acute pulmonary toxicity and inflammation induced by combined exposure to didecyldimethylammonium chloride and ethylene glycol in rats.

Didecyldimethylammonium chloride (DDAC), an antimicrobial agent, has been reported to induce pulmonary toxicity in animal studies. DDAC is frequently used in spray-form household products in combination with ethylene glycol (EG). The purpose of this study was to evaluate the toxic interaction between DDAC and EG in the lung. DDAC at a sub-toxic dose (100 µg/kg body weight) was mixed with a non-toxic dose of EG (100 or 200 µg/kg body weight), and was administrated to rats via intratracheal instillation. Lactate dehydrogenase activity and total protein content in the bronchoalveolar lavage fluid (BALF) were not changed by singly treated DDAC or EG, but significantly enhanced at 1 d after treatment with the mixture, with the effect dependent on the dose of EG. Total cell count in BALF was largely increased and polymorphonuclear leukocytes were predominantly recruited to the lung in rats administrated with the mixture. Inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6 also appeared to be increased by the mixture of DDAC and EG (200 µg/kg body weight) at 1 d post-exposure, which might be associated with the increase in inflammatory cells in lung. BALF protein content and inflammatory cell recruitment in the lung still remained elevated at 7 d after the administration of DDAC with the higher dose of EG. These results suggest that the combination of DDAC and EG can synergistically induce pulmonary cytotoxicity and inflammation, and EG appears to amplify the harmful effects of DDAC on the lung. Therefore pulmonary exposure to these two chemicals commonly found in commercial products can be a potential hazard to human health.

Evaluation of toxicity to triclosan in rats following 28 days of exposure to aerosol inhalation.

The present study was conducted to investigate the potential subchronic toxicity of triclosan (TCS) in rats following 28 days of exposure by repeated inhalation. Four groups of six rats of each sex were exposed to TCS-containing aerosols by nose-only inhalation of 0, 0.04, 0.13, or 0.40 mg/L for 6 h/day, 5 days/week over a 28-day period. During the study period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. At 0.40 mg/L, rats of both sexes exhibited an increase in the incidence of postdosing salivation and a decrease in body weight. Histopathological alterations were found in the nasal septum and larynx. There were no treatment-related effects in rats of either sex at ⩽0.13 mg/L. Under the present experimental conditions, the target organs in rats were determined to be the nasal cavity and larynx. The no-observed-adverse-effect concentration in rats was determined to be 0.13 mg/L.