Monitoring and identification of airborne asbestos in unorganized sectors, India.

Rajasthan state in India is credited to cater more than 90% of total production of asbestos in this country, of which around 60% is processed there in unorganized sectors including milling and manufacturing of asbestos-based products. Unorganized asbestos units particularly mills showed unhealthy occupational conditions, therefore industrial hygiene study was carried out focusing on the prevalence of asbestos fibres in air at work zone area of asbestos milling units. Fibre levels were in the range of 2.00-5.09f/cm(3) and 4.07-15.60f/cm(3) in unorganized asbestos mills of Rajasthan located at Beawer and Deogarh districts, respectively. Like asbestos concentration, fibre type and length are also vital factors in the health risk assessment of industrial workers. Phase contrast and polarized light microscopic study of asbestos fibres showed their amphibole nature registering about 90% as tremolite and rest as anthophyllite. Fibre length measured micrometrically were sub-grouped in <10microm, 11-20microm, 21-30microm and >30microm. About 30-40% fibres belonged to sub-group <10microm. It is concluded that unorganized asbestos mills bear poor industrial unhygienic conditions reflected specifically from their manyfold higher fibre concentrations than the Indian and International standards. Poor industrial unhygienic conditions are attributable to obsolete milling technology, lack of pollution control devices and escape from regulatory control.

Toxic responses in primary rat hepatocytes exposed with occupational dust collected from work environment of bone-based industrial unit.

In this in vitro study we investigated the toxic responses in hepatocytes treated with occupational dust to which workers are exposed in bone-based industrial units. The present study investigated the toxicity mechanism of bone-based occupational dust, from a particular industrial unit, on isolated rat hepatocytes. The hepatocytes were isolated by collagenase perfusion method and cell viability was determined by trypan blue exclusion and MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay treated with occupational dust at 0.1-1.0 mgmL(-1), for 120 min. The cell viability decreased significantly in a concentration-dependent manner. Dust induced significant membrane damage measured by lactate dehydrogenase (LDH) and glutathione (GSH) release in culture media for 30-, 60- and 120 min treatment duration. The toxicity was found to be correlated with the induction of lipid peroxidation (LPO). In addition, nitric oxide (NO), and hydrogen peroxide (H(2)O(2)) generation by occupational dusts were also found to be time- and concentration-dependent. Over all the present study provides initial evidences for the toxic potential of occupational dust generated in bone-based industries and, therefore, the dust exposure to workers in unorganized industrial units should be controlled.

Nano-talc stabilizes TNF-alpha m-RNA in human macrophages.

Particle size reduction of talc from micro- to nanoscale gradually enhanced its cytotoxicity however its inflammatory potential is still not explored. In the current study we observed increased TNF-alpha, IL-1beta and IL-6 mRNA levels in macrophages exposed to Nano-Talc (NT). Further, NT particles also showed constituent phosphorylation of both p38 and ERK1/2 pathway however JNK phosphorylation was transient. Pre-treatment of macrophages with p38 and ERK1/2 inhibitors either alone or in combination showed significant reduction in TNF-alpha mRNA stability, clearly suggesting their role in TNF-alpha mRNA stabilization and expression. Our observations clearly demonstrated the inflammatory potential of NT particles which might be at least partial and potential mechanism in talc mediated pathogenecity in the exposed population.

Nanotoxicity of dolomite mineral of commercial importance in India.

The risk of occupational exposure to dolomite, an important mineral exists both in organized as well as unorganized sectors. Toxicological profiles of bulk dolomite are meagerly known in general and its nanotoxicity in particular. Effects of micro- and nano particles on cell viability, LDH leakage and markers of oxidative stress were observed. The study indicated that cytotoxicity of dolomite nanoparticles is significantly higher than the microparticles. The study thus suggests for the prescription of exposure limit for nanodolomite in the best interest of health of workers at risk of exposure under mining, milling and industrial environment.

Ubiquitous hazardous metal lead induces TNF-α in human phagocytic THP-1 cells: primary role of ERK 1/2.

Induction of tumor necrosis factor-α (TNF-α) in response to lead (Pb) exposure has been implicated in its immunotoxicity. However, the molecular mechanism by which Pb upregulates the level of TNF-α is wagely known. An attempt was therefore made to elucidate the mechanistic aspect of TNF-α induction, mainly focusing transcriptional and post transcriptional regulation via mitogen activated protein kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic THP-1 cells resulted in significant enhanced production of TNF-α m-RNA and protein secretion. Moreover, the stability of TNF-α m-RNA was also increased as indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb exposed THP-1 was also evident. Specific inhibitor of ERK1/2, PD 98059 caused significant inhibition in production and stability of TNF-α m-RNA. However, SB 203580 partially inhibited production and stability of TNF-α m-RNA. Interestingly, a combined exposure of these two inhibitors completely blocked modulation of TNF-α m-RNA. Data tends to suggest that expression and stability of TNF-α induction due to Pb exposure is mainly regulated through ERK. Briefly, these observations are useful in understanding some mechanistic aspects of proinflammatory and immunotoxicity of Pb, a globally acknowledged key environmental contaminant.

Elevated blood lead levels and cytogenetic markers in buccal epithelial cells of painters in India: genotoxicity in painters exposed to lead containing paints.

BACKGROUND, AIM, AND SCOPE: Lead, a major contaminant, is highly used in paint manufacturing due to its anticorrosive properties. Recent reports indicated high lead content among Indian paints used for commercial purposes. Painters are continuously exposed to these lead containing paints during painting of both commercial as well as residential buildings. Lead is well-known for its genotoxicty in occupational workers; however, in Indian painters the genotoxic effects of lead have not been reported to date. Therefore we aimed to study the genotoxic end points in painters due to their long-term exposure to these high lead-containing Indian paints. MATERIALS AND METHODS: Study group selection was made after a questionnaire administration, which included questions about lifestyle and medical history to exclude exposure to the other potential sources of genotoxics. Blood and buccal cell samples were obtained from 30 male painters and from a similar number of age-matched controls of same location with no occupational exposure to lead. Blood lead levels (Pb-B) were measured in painters and controls. Micronucleus (MN) frequencies and nuclear changes, i.e., karyorrhexis, karyolysis, broken egg, and binucleated, were investigated in buccal epithelial cells. RESULTS: Painters had significantly (P < 0.01) greater lead levels in blood than the control group. MN frequencies and nuclear changes in buccal epithelial cells were also significantly (P < 0.01) elevated in painters as compared with control subjects. Regression analysis also revealed significant (P < 0.01) association of Pb-B with all the genotoxic endpoints in painters. Cytogenetic damage was significantly associated with Pb-B as no other co-founding factors (smoking, alcohols) showed significant difference between both groups. DISCUSSION: Lead is widely used in paints which may serve as potential source of exposure among painters due to their long-term engagement with paints. Our results clearly demonstrated genotoxicity among the exposed population as evident from increase micronucleus frequencies, frequent nuclear changes, and apoptosis. Many studies had previously related nuclear change events in buccal epithelial cells with the progression of different carcinomas. Furthermore in-depth investigations with larger sample size are needed to provide evidence to this effect. CONCLUSIONS: Here, we report cytogenetic toxicity to the exposed population by the high lead containing paints from India for the first time. Frequent, high and unregulated use of lead in paints may cause genetic mutation and may accelerate cytogenetic damage which may further lead to different carcinomas in painters. These findings need to be considered and necessary steps should be taken to protect the occupational workers engaged with these high lead-containing paints. RECOMMENDATIONS: The use of lead in paints is completely unregulated in India and routine surveillance of paints for lead content is still lacking. These paints are readily available in markets and are also used in other products (jewelry, miniblinds) which could be exported to other countries including United States and Europe. Serious consideration should be given to the inclusion of regulations and bans on the use of lead in paints. Moreover, attention should also be paid towards the use of various protective measures (face-masks, hand gloves, and separate clothes) by the workers as safe work practices during working periods.

The primary role of iron-mediated lipid peroxidation in the differential cytotoxicity caused by two varieties of talc nanoparticles on A549 cells and lipid peroxidation inhibitory effect exerted by ascorbic acid.

Talc particles, the basic ingredient in different kinds of talc-based cosmetic and pharmaceutical products, pose a health risk to pulmonary and ovarian systems due to domestic and occupational exposures. Two types of talc nanoparticles depending on the source of geographical origin - indigenous- and commercial talc nanoparticles were assessed for their potential in vitro toxicity on A(549) cells; along with indigenous conventionally used microtalc particles. Cell viability, determined through live/dead staining and 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, decreased as a function of concentration, origin and size of particles. Both varieties of talc nanoparticles differentially induced lipid peroxidation (LPO), which was correlated with the pattern of lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) generation, and glutathione (GSH) depletion. Relatively higher cytotoxicity of indigenous nanotalc could be attributed to its higher content of iron as compared to commercial nanotalc. The known scavenger of ROS, l-ascorbic acid significantly inhibited LPO induction due to talc particles. Data suggest that nanotalc toxicity on A(549) cells was mediated through oxidative stress, wherein role of iron-mediated LPO was much pronounced in differential cytotoxicity.

Nanotoxicity of pure silica mediated through oxidant generation rather than glutathione depletion in human lung epithelial cells.

Though, oxidative stress has been implicated in silica nanoparticles induced toxicity both in vitro and in vivo, but no similarities exist regarding dose-response relationship. This discrepancy may, partly, be due to associated impurities of trace metals that may present in varying amounts. Here, cytotoxicity and oxidative stress parameters of two sizes (10 nm and 80 nm) of pure silica nanoparticles was determined in human lung epithelial cells (A549 cells). Both sizes of silica nanoparticles induced dose-dependent cytotoxicity as measured by MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and lactate dehydrogenase (LDH) assays. Silica nanoparticles were also found to induce oxidative stress in dose-dependent manner indicated by induction of reactive oxygen species (ROS) generation, and membrane lipid peroxidation (LPO). However, both sizes of silica nanoparticles had little effect on intracellular glutathione (GSH) level and the activities of glutathione metabolizing enzymes; glutathione reductase (GR) and glutathione peroxidase (GPx). Buthionine-[S,R]-sulfoximine (BSO) plus silica nanoparticles did not result in significant GSH depletion than that caused by BSO alone nor N-acetyl cysteine (NAC) afforded significant protection from ROS and LPO induced by silica nanoparticles. The rather unaltered level of GSH is also supported by finding no appreciable alteration in the level of GR and GPx. Our data suggest that the silica nanoparticles exert toxicity in A549 cells through the oxidant generation (ROS and LPO) rather than the depletion of GSH.