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Urinary elimination of styrene in experimental and occupational exposure.

Twenty human volunteers were exposed to styrene vapor at 273-1 654 mumol/m3 (28.4-172.3 mg/m3) for a period of 1 to 3 h at rest (15 cases) and during light physical exercise (5 cases). Subsequently 51 workers occupationally exposed to styrene were studied during a workweek (median value 1 138 mumol/m3, geometric standard deviation 2.23). As expected, the relative uptake averaged about 65%, and the ratio of the alveolar concentration to the time-weighted average of the environmental concentration averaged about 0.15. Both in the experimentally exposed subjects and in the occupationally exposed workers the urinary styrene concentration showed a linear relationship to the corresponding environmental time-weighted average concentration. The correlation coefficients of the regression lines ranged between 0.88 (occupationally exposed group) and more than 0.93 (experimentally exposed groups). The regression coefficients were closely linked to the amount of styrene taken up and to the exposure times. The findings show that the urinary styrene concentration can be used as an appropriate biological exposure indicator whose meaning differs from that of other suggested indices. As an example, in occupationally exposed subjects performing moderate work the urinary styrene concentration corresponding to the time-weighted average of the threshold limit value is 815 nmol/l, and the 95% lower confidence limit (biological threshold) is 740 nmol/l.

Adult↗

Effect of subchronic inhalation exposure to low-level trichloroethylene on heart rate and wakefulness-sleep in freely moving rats.

Electroencephalographic (EEG) and heart rate (HR) responses to repeated 8-h exposure for 6 weeks to trichloroethylene (TRI) vapor of 50, 100 and 300 ppm were examined in freely moving rats with chronically implanted electrodes for polygraphic recordings. Exposure to all the TRI levels significantly decreased amount of time spent in wakefulness (W) during the exposure period. Exposure to 100 ppm and higher levels significantly decreased the time-averaged HR during the post-exposure period. The HRs during the stages of slow-wave sleep (SWS) and paradoxical sleep (PS) were significantly lowered after cessation of exposure to 50 ppm. When compared with the previously reported responses to short-term exposure to TRI (Arito H, et al. Arch Toxicol 1993; 67: 193-199), significant changes in wakefulness-sleep and HR elicited by the long-term exposure appeared at lower exposure levels. The EEG and HR effects of long-term exposure to TRI of 50 ppm or higher levels are discussed for their causative factors on the basis of the reported findings and for validity of the ongoing biological exposure limit value of TRI with reference to documentations enlisted for ACGIH's TLV of 50 ppm (ACGIH. Documentation of the threshold limit values and biological exposure indices, 5th ed. 1986: 595-597).

Animals↗

Physicochemical properties of nonreactive volatile organic chemicals to estimate RD50: alternatives to animal studies.

This article presents the correlations obtained between the results on the potency of nonreactive airborne chemicals as sensory irritants and several of their physicochemical properties. The potency of airborne sensory irritants obtained from a reflexively induced decrease in respiratory frequency has been measured in the past using mice. Typically, their potency has been expressed as the exposure concentration necessary to decrease respiratory frequency by 50% (RD50). A large database of RD50 values is now available and such values are highly correlated with occupational exposure guidelines such as threshold limit values (TLVs). We used the nonreactive volatile organic chemicals from this database, for which relevant physicochemical variables are available or can be calculated. These variables were vapor pressure (P) or Ostwald gas-liquid partition coefficients (L). The liquids used for L values were n-hexadecane, octanol, N-formylmorpholine, tri-(2-ethylhexyl)phosphate, and olive oil. Excellent correlations were found between log RD50 and log P, as well as between log RD50 and log L16, log L(Oct), log L(NFM), log L(EHP), or log L(Oil). It follows that as an alternative to the bioassay, these physicochemical variables can be used to estimate RD50 of nonreactive volatile organic chemicals. Appropriate exceptions to general estimation of RD50 values from physicochemical variables are also presented, as well as the most appropriate estimates which can be obtained within homologous series.

Air Pollutants, Occupational↗

Carboxyhaemoglobin saturation in relation to smoking and various occupational conditions.

The effects of smoking and occupational conditions on COHb saturation were studied among employees on traffic duty, in restaurants, in iron foundries, and in an office. The subjects were 139 smokers and 152 nonsmokers working in the same environments. Changes in COHb saturation were observed in samples of blood obtained before and after the working period. Samples of air were collected during the working hours in restaurants, in foundries and in office, 190 samples in all, for the determination of content of CO. Among the nonsmokers there was no change in COHb saturation in restaurants and in office work. On traffic duty and in iron foundries the increase was significant, but the values after work were less than half the permitted occupational threshold limit value (TLV) level of 6 per cent units. In the smoking group the mean values of COHb saturation before work were about twice the mean COHb saturation in the nonsmokers after work. In office work and in foundries the mean COHb saturations after the work exceeded the permitted TLV.

Adolescent↗

Urinary excretion of tetrachloroethylene (perchloroethylene) in experimental and occupational exposure.

Fifteen human volunteers were exposed to tetrachloroethylene (perchloroethylene, tetrachloroethene) vapor at 3.6-316 mg/m3 for 2-4 hr at rest (10 cases) and during light physical exercise (5 cases). Subsequently, 55 workers who were occupationally exposed to tetrachloroethylene in eight commercial dry cleaning facilities were studied (median value, 66 mg/m3; geometric standard deviation, 3.15 mg/m3). In both the experimentally exposed subjects and occupationally exposed workers the urinary concentration of tetrachloroethylene showed a linear relationship to the corresponding environmental time-weighted average concentration. The findings indicate that the urinary concentration of tetrachloroethylene can be used as an appropriate biological exposure indicator. In occupationally exposed subjects performing moderate work, the urinary tetrachloroethylene concentration corresponding to the time-weighted average of the threshold limit value proved to be 120 mcg/L and its 95% lower confidence limit (biological threshold) 100 mcg/L. The effects of workload on the tetrachloroethylene urinary elimination are also accounted for.

Adult↗

Cell detachment and growth of fibroblasts as parameters for cytotoxicity of inorganic metal salts in vitro.

Eight inorganic metal compounds (AlCl3, Al(OH)3 gel, Al(OH)3 salt, SnCl2, ZnSO4, K2Cr2O7, CdCl2, HgCl2) were tested for their cytotoxic effect on an established hamster fibroblast line (BHK-21/C13) in vitro using a cell detachment assay and two different growth assays, the cloning efficiency and the cell number after 2 days subconfluent culture as parameters. The test conditions for these assays were optimized, including incubation period, application of test substance, growth conditions and data analysis. Aluminum, zinc and tin compounds showed low cytotoxic effects when compared to potassium, cadmium and mercuric compounds. Potassium dichromate was highly toxic in both growth assays (0.0001-0.01 mM, with a clear dependency on the incubation time), whereas it proved to be only slightly toxic in the detachment assay (0.1-5 mM). Cadmium and mercuric chlorides were the most toxic compounds in the growth (0.00001-0.001 mM) and the cell detachment assays (0.01-0.1 mM). Variable incubation periods barely affected the cytotoxicity of mercuric chloride. Ranking of these cytotoxicity data was found to be identical to the ranking of LD50 values (oral, rat) as well as to the ranking according to threshold limit values for human workroom environment, and of human eye irritation data.

Aluminum↗

Assessment of vinyl chloride-induced DNA damage in lymphocytes of plastic industry workers using a single-cell gel electrophoresis technique.

DNA damage and the formation of stable carcinogen-DNA adducts are considered critical events in the initiation of the carcinogenic process. This study was carried out to assess whether exposure of plastics industry workers to the vinyl chloride monomer (VCM) for different periods of time would cause DNA damage, using the single-cell gel electrophoresis (SCGE) technique. Levels of DNA damage was assessed by both extent of DNA migration and numbers of DNA damaged spots in the peripheral blood lymphocytes from 32 plastics workers with different periods of exposure to VCM; they were evaluated by comparison with a group of non-exposed individuals. It was found that plastics workers who were exposed to VCM for different periods of time showed significantly increased levels of DNA damage compared with the non-exposed subjects. There was a significant correlation between the severity of DNA damage and duration of exposure. However, no significant correlation was found between the age of all subjects and DNA damage. Concentrations of VCM in the air inside the factory were found to be significantly higher than values in non-exposed areas, despite being lower than the threshold limit value (TLV). Our results encourage the application of SCGE as a sensitive, simple, fast and useful technique in the regular health screening of workers occupationally exposed to VCM (even at concentrations below the TLV) to assess the possibility of any DNA damage.

Adult↗

House-dust mite exposure reduction in specially designed, mechanically ventilated "healthy" homes.

Exposure to house-dust mites (Dermatophagoides spp.) was investigated in 30 asthmatic patients before and after moving to homes with mechanical ventilation systems. Median house-dust mite concentration was 110 mites per gram of mattress dust at the initial investigation and 20 mites per gram at the first follow-up after a mean of 4.7 months in the new homes. This was lower (P < 0.05) than counts in a control group of 23 asthmatic patients that had unchanged counts. At a second follow-up, after 15.0 months, mite counts in the study group were further reduced (P < 0.01) from initial values. Among 16 patients, with initial mite counts above the recommended threshold limit value (TLV) of 100 mites per gram of dust, the mite counts fell, in most cases, below this TLV. Air-exchange rates increased (P < 0.001) from a median value of 0.40 air changes per hour (ach) to 1.52 ach at the second follow-up investigation. Furthermore, a reduction (P < 0.01) was found in indoor absolute air humidity, with a median value of 5.6 g of water/kg. No such changes were found in the control group. The present study indicates that reduction of air humidity through an increased supply of fresh air may significantly diminish and, in some cases, even eliminate house-dust mites in homes.

Air Conditioning↗

1,1,1-Trichloroethane (methyl chloroform) in urine as biological index of exposure.

Fifteen human volunteers were exposed to 1,1,1-trichloroethane (methyl chloroform) vapor at 72-495 mg/m3 for a period of 2 to 4 hours at rest (ten cases) and during light physical exercise (five cases). Subsequently 60 workers occupationally exposed to 1,1,1-trichloroethane in a refrigerator manufacturing plant were studied (median value: 178 mg/m3; geometrical standard deviation: 2.19 mg/m3). As expected, the relative uptake (R) of 1,1,1-trichloroethane decreased in the course of exposure at rest (R = 0.44 after 20 minutes of exposure; R = 0.26 after 240 minutes of exposure). Both in the experimentally exposed subjects and in the occupationally exposed workers, the urinary concentration of 1,1,1-trichloroethane showed a linear relationship to the corresponding environmental time-weighted average concentration. The correlation coefficients (r) were 0.95 in occupationally exposed subjects and more than 0.90 in experimentally exposed groups. A linear equation also existed between urinary concentration and amount of 1,1,1-trichloroethane absorbed (r = 0.88). The findings indicate that the urinary concentration of 1,1,1-trichloroethane can be used as an appropriate biological exposure indicator. In occupationally exposed subjects performing moderate work, the urinary 1,1,1-trichloroethane concentration corresponding to the time-weighted average of the threshold limit value was found to be 860 micrograms/L and its 95% lower confidence limit (biological threshold) 805 micrograms/L.

Adult↗

Biological monitoring of occupational exposure to different chromium compounds at various valency states.

Chromium concentrations in the air were measured in seven different workroom environments, where exposure to water soluble hexavalent or trivalent compounds was expected. Urinary excretion of chromium was measured before and after the same arbitrarily chosen working day. End-of-shift urinary chromium and its increase above pre-exposure levels were closely related to the concentration of water soluble chromium (VI) in the air. The values corresponding to 50 micrograms m-3 in the air, which is the current threshold limit value in most countries, were 29.8 and 12.2 micrograms g-1 of creatinine, respectively. Urinary chromium in workers exposed to water insoluble chromates or to water soluble chromic (III) sulphate was definitely higher than that observed in subjects not occupationally exposed to chromium compounds, but it cannot be recommended as short-term exposure test for evaluation of the job-related hazard.

Absorption↗

Application of statistical models to estimate the correlation between urinary benzene as biological indicator of exposure and air concentrations determined by personal monitoring.

This study evaluated the correlation between benzene in urine and in workplace air at low airborne benzene levels (below 1 ppm). Eleven workers were monitored over a period of 1-4 days at a petrochemical plant in Italy; samples of end-of-shift urine and workplace air were analyzed for benzene. A significant correlation, with a coefficient of determination R(2)=0.63, was found between urine and airborne benzene, confirming the results of previous studies. Two different statistical models were utilized to estimate urine benzene values of 9-16 microg/L corresponding to the American Conference of Governmental Industrial Hygienists' threshold limit value (TLV) of 0.5 ppm in workplace air. Not withstanding the variability inherent to biological monitoring, the results suggest application of biomonitoring as a trigger for identification of lower exposure level below, but approaching the TLV. Additionally, the proposed benzene biomonitoring may be useful in evaluating PPE effectiveness and use characteristics as well as dermal contribution to total exposure.

Adult↗

Toxic effects of chemicals on mouse post-blastocyst development--a trial to establish a testing system for embryotoxicity.

We established a new testing system to assess embryotoxic chemicals using cultured preimplantation mouse embryos. Randomly bred Crj:CD-1 (ICR) mice were used. Late blastocysts collected on Day 4 of pregnancy (plug day:Day 1) were exposed for 24 hrs. to various chemicals at varying concentrations. Morphological embryonic development, structural chromosome aberrations and sister chromatid exchanges (SCEs) were examined as the parameters of embryotoxicity. Treated embryos were then transferred to pseudopregnant foster mice for the evaluation of in vivo development. Of the morphological developmental endpoints in vitro, the formation of two-layer ICMs (inner cell masses) was the most sensitive to the toxicity of chemicals, followed by ICMs and trophoblast outgrowth. Threshold limit values were confirmed regarding morphological growth. However, exposure of embryos to lower concentrations than threshold enhanced the frequency of chromosome aberrations and SCEs. Transfer of embryos treated with the lower concentration of 4-nitroquinoline 1-oxide induced not only fetal wastage but also developmental retardation. 4-nitroquinoline 1-oxide was the most embryotoxic in mouse blastocysts, followed in order by mitomycin C, bleomycin, methylmercuric chloride, diethylstilbestrol, mercuric chloride and ochratoxin-A. This new testing system appears to be a sensitive method of measuring the direct effects of toxic chemicals which yields results in a short term.

4-Nitroquinoline-1-oxide↗

Respiratory effects of a synthetic metalworking fluid and its components.

A synthetic metalworking fluid, MWF "A", and its major components were evaluated using a previously developed mouse bioassay. This fluid and its components evoked sensory (S) and pulmonary (P) irritation in mice. For MWF "A" and each of its components, a concentration-response relationship was developed on the basis of respiratory frequency (fR) responses. From such relationships, the concentration capable of evoking a 50% decrease in mean fR was determined for MWF "A" and each component (RD50). RD50S or RD50P was used to distinguish decreases in fR that were due to sensory irritation (S) from those due to pulmonary irritation (P). From RD50P values, it was concluded that the fatty acid alkanolamide condensates, tolutriazole, and triazine-type biocide components were similar in potency to one another and similar in potency to MWF "A". By examining potency and fractional composition, it was concluded that the fatty acid alkanolamide condensates and the triazine-type biocide largely contributed to the irritancy of MWF "A". From RD50P values, occupational exposure limits were proposed for MWF "A" and each of its components. The current Threshold Limit Value of 10 mg/m3 established by the American Conference of Governmental Industrial Hygienists for "particulates not otherwise classified" (PNOC) would be inadequate to protect workers from the irritating properties of MWF "A" and most of its components.

Aerosols↗

[Pollution of the work environment by volatile anesthetics and nitrous oxide].

Anaesthetic personnel is exposed to different workload conditions. The individual impact is influenced by external factors and human stress stability. Different symptoms reported to be present in anaesthetic personnel are comparable to symptoms of the sick building syndrome, defined by the WHO in the 90's. They are caused by work-induced distress and the exposure to chemical hazards. In anaesthesia, health defects by anaesthetic vapours and gases have been deplored for many years. After the Russian anaesthesiologist Vaisman published a report in 1967, controlled studies concerning cancerogenicity and teratogenicity of volatile anaesthetics under workspace conditions were carried out. In 1989, time-weighted average exposure threshold limit values of 5 ppm were released in the Federal Republic of Germany for halothane. In 1993 thresholds for enflurane (20 ppm) and nitrous oxide (100 ppm) were released. TLV concentrations for the new anaesthetic agents desflurane and sevoflurane have not yet been defined by authorities. Factors influencing workplace concentrations of anaesthetic gases are the anaesthetic procedures, apparatus leakage, air conditioning, fresh gas flow and the function of the scavenging system. Although cancerogenicity, mutagenicity, teratogenicity and reduction of fertility are discussed as effects of chronic exposure to anaesthetic gases, several review articles doubted the results of studies, finding positive correlations of incidence of occupational disease and the exposure to the volatile and gaseous substances. Mainly coexisting factors like smoke-induced exposure to polybromated biphenyls, disturbance in circadian rhythm, stress and enclosure in narrow exposure systems, increasing teratogenicity and cancerogenicity in animal experiments, are considered to promote unreliability of the studies. All reviewers do not discuss the fact, that all of these co-factors are present in the reality of the anaesthetic workplace. Thus, the studies by Corbett, enthusiastically criticized by different reviewers, simulate the all-day reality of the anaesthetic workplace more precisely than controlled experiments conducted, for example, by Eger and co-workers. The results of animal experiments and retrospective studies therefore do not justify realization of large controlled prospective studies but require the overall revision of the anaesthesiological workplace and the reduction of occupational waste gas exposure to the lowest possible levels below all chronic exposure threshold values.

Air Pollutants, Occupational↗

Biological monitoring in the occupational setting--relationship to cadmium exposure.

Statutory health surveillance of occupational exposure to cadmium exists in most Western countries. For biological monitoring, both indicators of internal dose and indicators of effect are available. Cadmium in urine is an indicator of chronic exposure and essentially reflects the body burden under low-exposure conditions and in the absence of renal damage. Whole blood cadmium is primarily a useful indicator for use in evaluations of recent exposures. Biological threshold limit values for cadmium in urine and blood are based on the correlation of biological levels with thresholds for renal dysfunction. The use of markers of high and low molecular weight proteinuria should be integrated into the health surveillance of cadmium-exposed workers. Priority should be given to the determination of albumin and of proteins such as beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin. Interpretation of biological monitoring data in terms of the threshold values requires a programme of periodic biological, medical and environmental monitoring.

Cadmium↗

Exposure-related health effects of silver and silver compounds: a review.

A critical review of studies examining exposures to the various forms of silver was conducted to determine if some silver species are more toxic than others. The impetus behind conducting this review is that several occupational exposure limits and guidelines exist for silver, but the values for each depend on the form of silver as well as the individual agency making the recommendations. For instance, the American Conference of Governmental Industrial Hygienists has established separate threshold limit values for metallic silver (0.1 mg/m3) and soluble compounds of silver (0.01 mg/m3). On the other hand, the permissible exposure limit (PEL) recommended by the Occupational Safety and Health Administration and the Mine Safety and Health Administration and the recommended exposure limit set by the National Institute for Occupational Safety and Health is 0.01 mg/m3 for all forms of silver. The adverse effects of chronic exposure to silver are a permanent bluish-gray discoloration of the skin (argyria) or eyes (argyrosis). Most studies discuss cases of argyria and argyrosis that have resulted primarily from exposure to the soluble forms of silver. Besides argyria and argyrosis, exposure to soluble silver compounds may produce other toxic effects, including liver and kidney damage, irritation of the eyes, skin, respiratory, and intestinal tract, and changes in blood cells. Metallic silver appears to pose minimal risk to health. The current occupational exposure limits do not reflect the apparent difference in toxicities between soluble and metallic silver; thus, many researchers have recommended that separate PELs be established.

Argyria↗

Occupational exposure limits for 30 organophosphate pesticides based on inhibition of red blood cell acetylcholinesterase.

Toxicity and other relevant data for 30 organophosphate pesticides were evaluated to suggest inhalation occupational exposure limits (OELs), and to support development of a risk assessment strategy for organophosphates in general. Specifically, the value of relative potency analysis and the predictability of inhalation OELs by acute toxicity measures and by repeated oral exposure NOELs was assessed. Suggested OELs are based on the prevention of red blood cell (RBC) acetylcholinesterase (AChE) inhibition and are derived using a weight-of-evidence risk assessment approach. Suggested OEL values range from 0.002 to 2 mg/m(3), and in most cases, are less than current permissible exposure levels (PELs) or threshold limit values(R) (TLVs(R)). The available data indicate that experimental data for most organophosphates evaluated are limited; most organophosphates are equally potent RBC AChE inhibitors in different mammalian species; NOELs from repeated exposure studies of variable duration are usually equivalent; and, no particular grouping based on organophosphate structure is consistently more potent than another. Further, relative potency analyses have limited usefulness in the risk assessment of organophosphates. The data also indicated that equivalent relative potency relationships do not exist across either exposure duration (acute vs. repeated) or exposure route (oral vs. inhalation). Consideration of all variable duration and exposure route studies are therefore usually desirable in the development of an OEL, especially when data are limited. Also, neither acute measures of toxicity nor repeated oral exposure NOELs are predictive of weight-of-evidence based inhalation OELs. These deviations from what is expected based on the common mechanism of action for organophosphates across exposure duration and route - AChE inhibition - is likely due to the lack of synchrony between the timing of target tissue effective dose and the experimental observation of equivalent response. Thus, comprehensive interpretation of all toxicity data in the context of available toxicokinetic, toxicodynamic and exposure information for each individual organophosphate in a weight-of-evidence based risk assessment is desirable when deriving inhalation OELs.

Animals↗

Biological specimen bank for smelter workers.

The biological specimen bank was initiated by the department of Environmental Medicine and the department of Medicine at the University of Umeå in 1975. The aims of the bank are to collect information on trace elements in human organs. Special attention is focused on the influence of occupational exposure. Tissue samples are taken from deceased workers from a copper and lead smelter in northern Sweden. Control specimens have been collected from deceased normal individuals from four control areas. Lung, liver and kidney samples are collected with quartz instruments and stored in quartz ampoules to avoid contamination. Other samples, e.g. bone, brain, fat, hair, heart muscle, nails, skin and stomach are taken with common autopsy instruments and stored in acid-washed polyethene vessels. The samples are stored at -20 degrees C. The elements Sb, As, Cd, Cr, Co, La and Se are analyzed by neutron activation analysis, Pb and Zn by atomic absorption spectrophotometry. The findings over time can be related to a number of factors: normal values in tissues, airborne exposure and causes of death. Special attention is paid variation over time, reevaluation of threshold limit values and risk assessment.

Autopsy↗