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The biology of talc.

Data are presented on the effects on health of talc dusts from exposure in industry and use of talc-containing health products. The mineralogy of talc and the composition of cosmetic and industrial grade talc dusts are described. Studies in animals are reviewed, and epidemiological data are considered in relation to exposures that occur during industrial and consumer uses of talc dusts. Hamsters exposed to 8 mg/m3 of respirable cosmetic grade talc dust for up to 150 minutes a day for 300 consecutive days showed no difference in incidence or nature of pathological lesions from those observed in a group of untreated animals. A retrospective study of the causes of death of 227 talc mine millers exposed to cosmetic grade talc at the threshold limit value for talc (20 million parts per cubic foot) for an average of 15-8 years showed that the causes of death were no different from those in a control cohort not exposed to talc dust. The available data indicate that talc dust exposure in the modern mining of cosmetic grade talc does not appear to be injurious to health. The significantly lower dust exposure in the normal use of cosmetic grade talc dusts in talc-containing health and cosmetic products confirms that their use is not a hazard to health.

Animals↗

Predictable "individual differences" in uptake and excretion of gases and lipid soluble vapours simulation study.

A five-compartment pharmacokinetic model with two excretory pathways, exhalation and metabolism, based on first order kinetics is used to outline the effect of body build, pulmonary ventilation, and lipid content in blood on uptake, distribution, and clearance of low solubility gases and lipid soluble vapours during and after exposure. The model shows the extent that individual differences have on altering uptake and distribution, with consequent changes in blood concentration, rate of excretion, and toxicity, even when variations in these parameters are within physiological ranges. The model is also used to describe the concentration variation of inhaled substances in tissues of subjects exposed to concentrations with permitted excursions. During the same course of exposure, the tissue concentrations of low solubility gases fluctuate much more than tissue concentrations of lipid soluble vapours. The fluctuation is reduced by metabolism of inhaled substance. These conclusions are recommended for consideration whenever evaluating the effect of excursions above the threshold limit values used in the control of industrial exposures (by excursion factors).

Body Constitution↗

Respiratory exposures associated with silicon carbide production: estimation of cumulative exposures for an epidemiological study.

Silicon carbide is produced by heating a mixture of petroleum coke and silica sand to approximately 2000 degrees C in an electric furnace for 36 hours. During heating, large amounts of carbon monoxide are released, sulphur dioxide is produced from residual sulphur in the coke, and hydrocarbon fume is produced by pyrolysis of the coke. Loading and unloading furnaces causes exposures to respirable dust containing crystalline silica, silicon carbide, and hydrocarbons. In the autumn of 1980 extensive measurements were made of personal exposures to air contaminants. Eight hour time weighted exposures to sulphur dioxide ranged from less than 0.1 ppm to 1.5 ppm and respirable participate exposures ranged from 0.01 mg/m3 to 9.0 mg/m3. Geometric mean particulate exposures for jobs ranged from 0.1 mg/m3 to 1.46 mg/m3. The particulate contained varying amounts of alpha-quartz, ranging from less than 1% to 17%, and most quartz exposures were substantially below the threshold limit value of 100 micrograms/m3. Only traces of cristobalite (less than 1%) were found in the particulate. Median exposures to air contaminants in each job were estimated. Since the operations at the plant had been stable over the past 30 years, it was possible to estimate long term exposures of workers to sulphur dioxide, respirable particulate, quartz, total inorganic material, and extractable organic material. Cumulative exposure (average concentration times exposure duration) for each of the air contaminants was estimated for each worker using his job history. There was sufficient independent variability in the sulphur dioxide and respirable particulate cumulative exposures to make an assessment of their independent effects feasible. The theoretical basis for using the cumulative exposure index and its shortcomings for epidemiological applications were presented.

Air Pollutants, Occupational↗

Exposure to oxides of nitrogen: respiratory symptoms and lung function in British coalminers.

Five hundred and sixty British coalminers with relatively high or relatively low exposures to oxides of nitrogen, based on measurements of concentrations of these gases at nine collieries over four years, and records of the men's places of work and colliery mining conditions over a total of eight years have been studied. Data on these men's respiratory symptoms and ventilatory capacity (FEV1), obtained as part of an epidemiological study of British coalminers, have been used to investigate possible adverse effects of exposure to oxides of nitrogen. Exposures to oxides of nitrogen were generally well below threshold limit values, though occasional peaks after shotfiring and during diesel locomotive use did exceed short term limits. No relationship was found between exposure and respiratory symptoms or decline in FEV1 nor was there any evidence of differences in symptoms of FEV1 between 44 pairs of men matched for age, dust exposure, smoking habit, coal rank, and type of work, but differing in respect of exposure to oxides of nitrogen. It has not been possible to detect any adverse effects on the health of this working population of the levels of nitrogen oxides that have occurred in British mines over the past decade. With the current levels of these gases, any long term effects on respiratory health are so small as to be undetectable in the presence of smoking and dust exposure.

Coal Mining↗

A cross sectional study of employees with potential occupational exposure to ethylene oxide.

A cross sectional study was conducted on 84 employees potentially exposed to ethylene oxide (EO) to determine whether they had a higher prevalence of abnormalities of the haematopoietic, hepatic, or renal systems than a control group individually matched on age, hire date, race, smoking habits, alcohol history, and date of examination. Potential exposures were estimated to be generally below the current threshold limit value of 10 ppm, with most below 1 ppm. Results of the haematological and biochemical studies were similar in the two groups. A statistically significant (p = 0.035) increase in the prevalence of proteinuria was noted among the EO group which warrants further investigation.

Blood Chemical Analysis↗

Acute exposure of symptomatic steelworkers to sulphur dioxide and carbon dust: effects on mucociliary transport, pulmonary function, and bronchial reactivity.

Nine steel workers participated in controlled exposures to sulphur dioxide alone and sulphur dioxide plus carbon dust (5 ppm and 10 mg/m3, respectively). All were experiencing work related respiratory difficulties. Bronchial clearance was measured using radioaerosol inhalations and external detection. Results were variable and no statistically significant changes were observed. One asthmatic showed a complete cessation of clearance during exposure to sulphur dioxide and carbon dust. Bronchial reactivity was found to be significantly raised after exposure to sulphur dioxide but equivocal results were found after exposure to sulphur dioxide and carbon dust. Pronounced changes in pulmonary function were seen only in the two asthmatic subjects. They could not tolerate the levels, indicating that these threshold limit values are too high, at least for these individuals who showed much greater sensitivity to the pollutants than the others.

Adult↗

Silicosis in jade workers.

The recent finding of cases of silicosis among jade workers in Hong Kong points to this disease being an occupational hazard. The source was found to be the silica flour that was added in a polishing process. Five cases are described together with the results of environmental investigation in a workplace. In three cases the disease was of early onset, rapidly progressive, and presented the features of galloping silicosis noted in other occupational exposures to silica flour. One patient had massive fibrosis and severe glomerulonephropathy, an association that has also been previously noted. One case showed evidence of active tubercular infection in addition to silicosis and two had healed lesions. Silica concentrations in the workplace during the suepect process were well above accepted threshold limit values.

Adult↗

Respiratory disease in foundry workers.

A survey was carried out in a steel foundry in Brisbane to evaluate the nature and frequency of respiratory symptoms and to assess ventilatory function. The foundry used many moulding processes including the Furane, Isocure, Shell, carbon dioxide, and oil sand systems. Nasal symptoms and wheeze were often reported, particularly by workers in the general foundry and core shop, and on a semiautomated line. By contrast, workers in the aftercast section not exposed to fumes or vapours from the various moulding processes reported these symptoms less often. Of 46 workers exposed to moulding fumes and vapours, 11 had developed a wheeze while working at the foundry. Wheeze and other respiratory tract symptoms were often attributed by the workers to exposure to substances at work, particularly from the Shell process which uses phenol formaldehyde resin and hexamethylenetetramine. Symptoms were reported also, but less often, on exposure to materials used in the Furane process (urea formaldehyde and furfuryl alcohol) and the Isocure process (methylene diphenyl diisocyanate, phenol formaldehyde, and dimethylethylamine). Ventilatory function studied over Monday and Friday showed a small and inconsistent changes. The six subjects working on the semiautomated line showed a small decrease in FEV1 (+/- SEM) (208 +/- 70 ml) only on Monday; this differed significantly from that in 17 aftercast workers (9 +/- 50 ml, p less than 0.05). Ventilatory function recorded before work on Monday morning showed no evidence of chronic airway obstruction in any group. Most environmental measurements were below the threshold limit values (TLV) except in the general foundry, where furfuryl alcohol was detected at concentrations of up to 50 ppm and formaldehyde at 4 ppm. The onset of symptoms in relation to exposure to various fumes and vapours suggests that both irritant and hypersensitivity mechanisms are present. As environmental modifications had occurred recently the apparent hypersensitivity may relate to past exposure levels above the TLV.

Adult↗

Coexposure to toluene and p-xylene in man: uptake and elimination.

Eight male subjects were experimentally exposed to toluene, p-xylene, and a combination of toluene and p-xylene in order to study the influence of coexposure and exposure to different levels of each solvent on their uptake and elimination. The exposures were performed for four hours at exposure levels equivalent to or lower than the Swedish threshold limit value for toluene, 300 mg/m3 (3.2 mmol/m3). During and after the exposure, solvent concentrations were measured in blood and in expired air. In addition, the pulmonary ventilation rate was measured during the exposure. Decreases in the blood/end exhaled air concentration ratio were found for both toluene and p-xylene when given in combination compared with separate exposure. The total solvent uptake relative to the exposure level was decreased after exposure to the higher solvent concentrations, and the apparent clearance was also decreased after exposure to the higher concentrations of solvent. Finally, the blood solvent concentrations were lower at the end of the exposure compared with the maximal concentration during each exposure condition. In the kinetics of toluene and p-xylene the total amount of toluene or p-xylene, or both, seems to be of major importance. The change in blood/end exhaled air concentration ratio may indicate an effect of coexposure.

Adult↗

Coexposure to toluene and p-xylene in man: central nervous functions.

Sixteen men were studied in an exposure chamber to assess the effect of four hours' exposure to toluene (3.25 mmol/m3), xylene (2.84 mmol/m3), a mixture of toluene and xylene (2.20 + 0.94 mmol/m3), and a control condition. With the aid of microcomputers, subjects performed tests of simple reaction time, short term memory, and choice reaction time immediately after entering the chamber, after two, and after four hours' exposure. The results indicate that the performance on the tests was unaffected by exposure. In the light of this result the risk of an acute effect on central nervous functions after exposure for four hours at concentrations that do not exceed the Swedish threshold limit values was considered to be minimal.

Adult↗

Normal serum activities of liver enzymes in Swedish paint industry workers with heavy exposure to organic solvents.

The serum activities of the liver enzymes alanine aminotransferase, aspartate aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase were examined in 47 paint industry workers and unexposed age matched referents. The workers were exposed to a mixture of industrial solvents, of which xylene was the main component in most cases. The median total exposure was about 50% of Swedish 1981 threshold limit values according to measurements of individual solvent exposure performed at the same time. No differences in enzyme activities were shown either when the whole exposed and referent groups were compared or when the five workers with outstanding solvent exposures of five times the TLV or more were compared with their referents. It is concluded that in most workers the liver seems to remain largely undamaged from inhalation exposure to a commonly used mixture of non-chlorinated solvents. In many workers this seems to hold true even for high exposures for limited periods.

Adult↗

Neurobehavioural effects of occupational exposure to lead.

A set of neurobehavioural tests selected on the basis of information processing theory was used to study the effect of low level occupational lead exposure on 59 lead workers compared with a matched control group of the same number. Only one of the lead exposed group had a blood lead concentration above the current threshold limit value of 3.81 mumol/l at the time of testing (mean 2.36 mumol/l, range 1.19-3.92 mumol/l) and none had been detected above that level in the previous three years. Nevertheless, most neurobehavioural functions tested showed some impairment in the lead workers. Visual sensory function was affected and, perhaps as a consequence, sustained attention and psychomotor tasks were performed more slowly by the lead exposed group. Cognitive functions were also impaired, with sensory store memory, short term memory, and learning abilities all showing deficits in lead workers. Such cognitive deficits may also be partly due to initial degradation of the visual input. Long term memory performance compared equally with control levels possibly because of development of a compensatory strategy such as rehearsal by the lead exposed subjects. Multiple linear regression analysis relating to lead workers test performance and their lead exposure showed that performance on the sensory store memory test alone was significantly related to exposure. This was probably due to the homogeneity of the lead exposed group with regard to blood lead concentrations and the use of blood lead as a measure of chronic lead exposure.

Adolescent↗

Incidence of cancer and mortality among employees in the asbestos cement industry in Denmark.

In a cohort study of the incidence of cancer and mortality among 7996 men and 584 women employed in the Danish asbestos cement industry between 1928 and 1984 over 99% were traced. Chrysotile asbestos was the only fibre type used until 1946, when amosite and (in 1952) crocidolite were also introduced. Chrysotile constituted 89%, amosite 10%, and crocidolite 1% of the asbestos used. During the first 25 years of manufacture the exposure levels were high, especially in areas where the asbestos was handled dry. Measurements from 1948 indicate that the fibre levels may have ranged from 100 to 1600 times over the present Danish threshold limit value of 0.5 fibre/ml. In 1973 more than 41% of personal samples were higher than 2 f/ml. About 76% of the workforce left the factory within five years of starting employment. A total of 1346 deaths and 612 cases of cancer were observed in the cohort between 1943 and 1984. Among employed men the overall mortality (O/E 1.18; 95% CI 1.12-1.25), cancer mortality (O/E 1.32; 95% CI 1.19-1.46), and overall incidence of cancer (O/E 1.22; 95% CI 1.12-1.32) were significantly increased compared with all Danish men. This was not so among employed women. For men, significant excess risks were found for cancer of the lung (O/E 1.80; 95% CI 1.54-2.10), pleura (O/E 5.46; 95% CI 2.62-10.05), mediastinum (O/E 5.00; 95% CI 1.01-14.61), stomach (O/E 1.43; 95% CI 1.03-1.93), and other male genital organs (O/E 3.03; 95% CI 1.11-6.60). The mortality was significantly increased for men for non-malignant pulmonary diseases (O/E 1.63; 95% CI 1.33-1.98). Among the group of asbestos cement workers with first employment 1928-40 an excess risk of laryngeal cancer was found (O/E 5.50;95% CI 1.77-12.82). A total of 12 cases of pleural and one of peritoneal mesotheliomas was observed when the original notification forms were reviewed for all patients with cancer in the cohort.

Asbestos↗

Special nerve functions and colour discrimination in workers with long term low level exposure to carbon disulphide.

Certain functions of the peripheral and autonomic nervous systems, and colour discrimination were examined in 45 workers (mean age 49; mean exposure to carbon disulphide (CS2) 20 years) and 37 controls (mean age 48). Conduction velocity and refractory period of the peroneal and sural nerves were determined. The conduction velocity of the slower fibres of the peroneal nerve was measured by means of an improved method that makes use of the refractory period. Function of autonomic nerves was assessed by measuring the variation in heart rate during rest, during deep breathing, and during isometric muscle contraction. Colour discrimination was evaluated by the Lanthony desaturated test. Individual cumulative exposure to CS2 was calculated on the basis of exposure in the past and individual job history. Mean cumulative exposure was 165 ppm-years. The peroneal nerves of exposed workers showed a decrease (-1.0 m/s) in conduction velocity of the slow fibres and a prolongation (0.1 ms) of the refractory period (mean 1.6 ms) compared with controls. These effects were related to cumulative exposure. No impairment of function of the sural nerve or of colour discrimination was found. The muscle heart reflex was decreased in the exposed group, but this was not related to cumulative exposure. This study has established more firmly that a decrease in conduction velocity of slow motor fibres occurs at low levels of exposure to CS2. Extrapolation of the results suggests that small effects may occur after 40 years of exposure to concentrations below the present threshold limit value (10 ppm).

Autonomic Nervous System↗

Exposure to peat dust: acute effects on lung function and content of bronchoalveolar lavage fluid.

Mechanised production of peat for fuel consumption is associated with high concentrations of organic dust, which is inhaled by the peat workers. In the present study 17 workers at two peat bogs in northern Sweden were examined. Personal sampling of total dust and the respirable fraction was performed during several workshifts. Dynamic spirometry was carried out before and at the end of shifts. Bronchoscopy with bronchoalveolar lavage (BAL) was performed in six subjects at the end of the working season and the results were compared with unexposed reference subjects. Peat workers using modern machines with ventilated cabins containing air filters were found to be exposed to low concentrations of peat dust. The recorded dust concentrations were below the threshold limit value for organic dust (5 mg/m3 air) in all but one worker. The respirable fraction of peat dust recorded in the breathing zone of the workers correlated significantly with a decrease in forced expiratory volume in one second (FEV1). The effect on lung function in non-asthmatic peat workers was, however, small. The concentration of lysozyme positive alveolar macrophages in BAL fluid was significantly lower in the peat workers compared with reference subjects. An inverse correlation was found between the mentioned cells and exposure to the respirable fraction of the peat dust. Furthermore, one particularly dust exposed worker had pronounced increases in alveolar macrophages, fibronectin concentration, and mast cells in BAL fluid.

Adolescent↗

Nerve function in workers with long term exposure to trichloroethene.

Certain functions of the nervous system were examined in 31 printing workers (mean age 44) exposed to trichloroethene (mean duration 16 years) and 28 controls (mean age 45). In the sural nerve the conduction velocity (SNCV), response amplitude, and refractory period (SRP) were measured. The latencies of the masseter and the blink reflex were determined to test the trigeminal nerve. In the peroneal nerve the conduction velocity of fast and slow nerve fibres, the response amplitude, and the refractory period were determined. As a measure of autonomic nerve function the response of the heart rate was determined to isometric muscle contraction and deep breathing. Individual cumulative exposure was calculated on the basis of exposure levels in the past. The mean cumulative exposure of the exposed workers was 704 ppm x years. For the assessment of the exposure effect relation a multiple linear regression model was used. A slight reduction (-1.1 m/s) in the SNCV was found and a prolongation (0.4 ms) of the SRP (mean of the controls 1.95 ms). The latency of the masseter reflex (mean 10.4 ms) had increased (0.4 ms). With respect to the blink reflex no prolongation was found. No impairment was found in the functions of motor and autonomic nerves. This study shows that the refractory period may be a sensitive indicator of preclinical toxic neuropathies. Long term exposure to trichloroethene at threshold limit values (about 35 ppm) may slightly affect the trigeminal and sural nerves.

Adult↗

Deposition of aluminium in tissues of rabbits exposed to inhalation of low concentrations of Al2O3 dust.

With strong evidence coming to light for the toxicity of aluminium (Al), especially to the brain, investigation into the effects of inhalation of low concentrations of Al dust in animal models has become important. This study follows up previous observations on the effects of Al on the concentrations of essential metals in serum of workers exposed to inhalation of low concentrations of Al dust, with a study of the concentrations of Al in tissues of rabbits exposed to Al dust at one twentieth of the threshold limit value (TLV). Even at this low concentration, the amount of Al in the brains of these animals was nearly two and a half times as high as that of the control animals. The concentrations in other tissues were similar to normal. At the same time, the concentrations of Al in the serum was only slightly raised, indicating that this variable is a poor marker for the effects of Al on the body. It is suggested that an extensive study is needed to determine a more correct TLV and health based permissible concentration for occupational exposure to Al.

Aluminum↗

The toxicity of benzene and its metabolism and molecular pathology in human risk assessment.

Benzene, a common industrial chemical and a component of gasoline, is radiomimetic and exposure may lead progressively to aplastic anaemia, leukaemia, and multiple myeloma. Although benzene has been shown to cause many types of genetic damage, it has consistently been classified as a non-mutagen in the Ames test, possibly because of the inadequacy of the S9 microsomal activation system. The metabolism of benzene is complex, yielding glucuronide and sulphate conjugates of phenol, quinol, and catechol, L-phenylmercapturic acid, and muconaldehyde and trans, trans-muconic acid by ring scission. Quinol is oxidised to p-benzoquinone, which binds to vital cellular components or undergoes redox cycling to generate oxygen radicals; muconaldehyde, like p-benzoquinone, is toxic through depletion of intracellular glutathione. Exposure to benzene may also induce the microsomal mixed function oxidase, cytochrome P450 IIE1, which is probably responsible for the oxygenation of benzene, but also has a propensity to generate oxygen radicals. The radiomimetic nature of benzene and its ability to induce different sites of neoplasia indicate that formation of oxygen radicals is a major cause of benzene toxicity, which involves multiple mechanisms including synergism between arylating and glutathione-depleting reactive metabolites and oxygen radicals. The occupational exposure limit in the United Kingdom (MEL) and the United States (PEL) was 10 ppm based on the association of benzene exposure with aplastic anaemia, but recently was lowered to 5 ppm and 1 ppm respectively, reflecting a concern for the risk of neoplasia. The American Conference of Governmental Industrial Hygienists (ACGIH) has even more recently recommended that, as benzene is considered an A1 carcinogen, the threshold limit value (TLV) should be decreased to 0.1 ppm. Only one study in man, based on nine cases of benzene associated fatal neoplasia, has been considered suitable for risk assessment. Recent re-evaluation of these data indicated that past assessments may have overestimated the risk, and different authors have considered that lifetime exposure to benzene at 1 ppm would result in an excess of leukaemia deaths of 9.5 to 1.0 per 1000. Although in this study, deaths at low levels of benzene exposure were associated with multiple myeloma and a long latency period, instead of leukaemia, which might justify further lowering of the exposure limit, the risk assessment model has been found to be non-significant for response at low levels of exposure. The paucity of data for man, the complexity of the metabolic activation of benzene, the interactive and synergistic mechanisms of benzene toxicity and carcinogenicity, the different disease endpoints (aplastic anaemia, leukaemia, and multiple myeloma), and different individual susceptibilities, all indicate that in such a complex scenario, regulators should proceed with caution before making further changes to the exposure limit for this chemical.

Anemia, Aplastic↗