Time-weighted Average Threshold Limit Value Research Articles

Glutaraldehyde Inhalation Exposure of Rats: Effects on Lung Morphology, Clara-Cell Protein, and Hyaluronic Acid Levels in BAL

Glutaraldehyde (GA) is a biocide widely used in hospital and laboratory practice. GA is a volatile substance and, under certain circumstances, significant airborne concentrations may be generated at room temperature. Occupational exposure to GA by inhalation is suspected of causing delayed irritating effects. In recent years, GA has emerged as the main cause of occupational asthma among health-care workers. The aim of the present study was to evaluate effects of GA inhalatory exposure (0.025 ppm or 0.1 ppm, for 28 days) in rats exposed corresponding to the occupational shift cycle, at time point 24 h, 48 h, and 7 days postexposure (PE). Numerous vacuoles and dilated spaces in epithelial cells in bronchioles showing a destructive effect of GA on the cellular membrane were observed at 24 h PE in 0.1 ppm exposed rats. Lipid vacuoles observed after 48 h PE in higher GA exposure, in the Clara cells of the bronchial epithelium, and in endothelial cells of the alveolar capillaries are probably attributable to disturbed lipid metabolism. Many foci of collagen fibers were observed already after 7 days postexposure. Monitoring of inflammatory response and repair was made possible by using two biomarkers: Clara-cell protein (CC16) and hyaluronic acid (HA). Our results show that the inflammatory repair response contributed to progenitor Clara cells and HA plays a role in the development of fibrotic changes in the lung of rats. Glutaraldehyde in rats causes fibrotic effects at the actual threshold limit value-time weighted average (TLV-TWA) level for GA as specified by current Polish and other national regulations.

Acute sensory irritation from exposure to isopropanol (2-propanol) at TLV in workers and controls: objective versus subjective effects.

Phlebotomists occupationally exposed to isopropanol (IPA) (2-propanol) and naïve controls (n = 12 per group) were exposed to the time-weighted average threshold limit value of 400 p.p.m. IPA for 4 h in an environmental chamber to investigate: (i) acute effects of sensory irritation using subjective health symptom reports and objective, physiological end-points; and (ii) differences in measured effects in relation to exposure history. Before, during and after exposure subjects gave self-reports of health complaints. During exposure subjects rated the intensity of the odor, sensory irritation and annoyance. Objective end-points of ocular hyperemia, nasal congestion, nasal secretion and respiration were obtained at various times before, during and after exposure. Results were compared with exposure to phenylethyl alcohol (PEA), a negative control for irritation, and to clean air (CA), a negative control for odor and irritation, using a within-subjects design. Significantly higher intensity ratings of odor, irritation and annoyance were reported during the exposure to IPA, when compared with exposure to CA or PEA. Nevertheless, the overall level of reported sensory irritation to IPA was low and perceived as 'weak' on average. Health symptom ratings were not significantly elevated for IPA as compared with PEA or CA exposure. The only physiological end-point that showed a change exclusively in the IPA condition was respiration frequency: relative to baseline, respiration frequency increased in response to IPA in both groups. No differences were encountered between the occupationally exposed and the control groups. The increase in respiration frequency in response to IPA may reflect either a reflexive change due to sensory irritation (an autonomic event) or a voluntary change in breathing in response to perception of an unpleasant, solvent-like odor (a physiological event caused by cognitive mediation). Our findings on objective end-points, including nasal and ocular sensory irritation, did not confirm subjective irritation reports. Irritation reports and odor intensity decreased, rather than increased, over time, lending credence to the cognitive argument and suggesting that the elevated subjective responses to IPA may be mediated by responses to its odor.

Absence of significant genotoxicity in lymphocytes and urine from workers exposed to moderate levels of cobalt-containing dust: A cross-sectional study

Mortality studies have shown that, in the past, lung cancer occurred after exposure to mixtures of cobalt metal and metallic carbide particles, the main constituents of hard metals, but apparently not when exposure was to cobalt alone. The major objective of this biomonitoring study was to assess genotoxic effects as a measure for carcinogenic risk in workers from cobalt refineries and hard metal plants currently exposed to the threshold limit value/time-weighted average (TLV-TWA) for cobalt-containing dust. The study comprised three groups of workers: 35 workers exposed to cobalt dust from three refineries, 29 workers exposed to hard metal dust from two producing plants, and 35 matched control subjects recruited from the respective plants. The study design integrated complementary methodologies to assess biomarkers of effects that represent both initial DNA damage (8-hydroxydeoxyguanosine [8-OHdG] in urine and comet assay on lymphocytes) and definitive chromosome breakage/loss (micronuclei in lymphocytes). Cobalt and cotinine were determined in urine as a measure for cobalt exposure and recent smoking, respectively. No significant increase of genotoxic effects was detected in workers exposed to cobalt-containing dust as compared to controls. No difference in any genotoxicity biomarker was found between workers exposed to cobalt and hard metal dusts. Multiple regression analysis indicated that workers who smoked and were exposed to hard metal dusts had elevated 8-OHdG and micronuclei values. Because this observation is in line with a previous epidemiological study of an increased risk of dying from lung cancer in workers from the hard metal industry who smoked, it is concluded that this specific occupational group needs closer medical surveillance.

Absence of significant genotoxicity in lymphocytes and urine from workers exposed to moderate levels of cobalt-containing dust: a cross-sectional study.

Mortality studies have shown that, in the past, lung cancer occurred after exposure to mixtures of cobalt metal and metallic carbide particles, the main constituents of hard metals, but apparently not when exposure was to cobalt alone. The major objective of this biomonitoring study was to assess genotoxic effects as a measure for carcinogenic risk in workers from cobalt refineries and hard metal plants currently exposed to the threshold limit value/time-weighted average (TLV-TWA) for cobalt-containing dust. The study comprised three groups of workers: 35 workers exposed to cobalt dust from three refineries, 29 workers exposed to hard metal dust from two producing plants, and 35 matched control subjects recruited from the respective plants. The study design integrated complementary methodologies to assess biomarkers of effects that represent both initial DNA damage (8-hydroxydeoxyguanosine [8-OHdG] in urine and comet assay on lymphocytes) and definitive chromosome breakage/loss (micronuclei in lymphocytes). Cobalt and cotinine were determined in urine as a measure for cobalt exposure and recent smoking, respectively. No significant increase of genotoxic effects was detected in workers exposed to cobalt-containing dust as compared to controls. No difference in any genotoxicity biomarker was found between workers exposed to cobalt and hard metal dusts. Multiple regression analysis indicated that workers who smoked and were exposed to hard metal dusts had elevated 8-OHdG and micronuclei values. Because this observation is in line with a previous epidemiological study of an increased risk of dying from lung cancer in workers from the hard metal industry who smoked, it is concluded that this specific occupational group needs closer medical surveillance.

Absence of prenatal developmental toxicity from inhaled arsenic trioxide in rats.

A review of the literature revealed no published inhalational developmental toxicity studies of arsenic performed according to modern regulatory guidelines and with exposure throughout gestation. In the present study, inorganic arsenic, as arsenic trioxide (As(+3), As2O3), was administered via whole-body inhalational exposure to groups of twenty-five Crl:CD(SD)BR female rats for six h per day every day, beginning fourteen days prior to mating and continuing throughout mating and gestation. Exposures were begun prior to mating in order to achieve a biological steady state of As(+3) in the dams prior to embryonal-fetal development. In a preliminary exposure range-finding study, half of the females that had been exposed to arsenic trioxide at 25 mg/m3 died or were euthanized in extremis. In the definitive study, target exposure levels were 0.3, 3.0, and 10.0 mg/m3. Maternal toxicity, which was determined by the occurrence of rales, a decrease in net body weight gain, and a decrease in food intake during pre-mating and gestational exposure, was observed only at the 10 mg/m3 exposure level. Intrauterine parameters (mean numbers of corpora lutea, implantation sites, resorptions and viable fetuses, and mean fetal weights) were unaffected by treatment. No treatment-related malformations or developmental variations were noted at any exposure level. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 3.0 mg/m3; the NOAEL for developmental toxicity was greater than or equal to 10 mg/m3, 760 times both the time-weighted average threshold limit value (TLV) and the permissible exposure limit (PEL) for humans. Based on the results of this study, we conclude that arsenic trioxide, when administered via whole-body inhalation to pregnant rats, is not a developmental toxicant.

Multiple exposure to arsenic, antimony, and other elements in art glass manufacturing.

Art glass manufacturing is one of the most interesting examples of exposure to complex mixtures. Among the raw materials used are silica sand, borax, carbonates, nitrates of Ca, Na, K, and a great number of compounds that are mainly oxides of As, Sb, Al, Zn, Cr, Ni, Sn, Se, Cd, Mn, Cu, Co, Fe, Nd, Er, Eu, and La. In six art glass factories that use As or Sb as fining agents, the exposure to these elements was investigated in 32 workers by means of environmental and biological monitoring. Analysis was conducted by atomic absorption spectrometry (AAS) and inductively coupled plasma mass spectrometry (ICP-MS). The results confirmed that As, which is the main carcinogen in glass production, reaches high air concentrations and is generally above the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value-time-weighted average (TLV-TWA) of 10 micrograms/m3. When partly substituted by antimonial compounds, As air concentrations dropped dramatically, while the air levels of Sb (which is considered less toxic but is classified as a class 2B carcinogen by IARC) were relatively low and below the ACGIH TLV-TWA of 500 micrograms/m3. Exposure to As and Sb also differed in the three types of jobs investigated: As was high in oven chargers, Sb was higher in batch mixers, and both elements were low in makers-formers. Eleven to 18 elements were detected: arsenic, Al, Ba, Sb, Pb, and Zn were the elements most frequently measured (in tens, and in some cases hundreds, of micrograms/m3), followed by B, Li, Mn, Se, Sn, Sr, Ce, La, and Nd (in micrograms or in some cases tens of micrograms/m3. The results of biological monitoring for As, Sb, and other elements were in agreement with environmental monitoring data. We concluded that multiple detection of elements is a useful tool (or the evaluation of exposure to complex mixtures such as those used in the art glass industry and that such detection also allows a more accurate evaluation of related epidemiological data.

Biological monitoring of triethylamine among cold-box core makers in foundries.

The objectives of the study were to assess triethylamine (TEA) exposure in cold-box core making and to study the applicability of urinary TEA measurement in exposure evaluation. Air samples were collected by pumping of air through activated-charcoal-filled glass tubes, and pre- and postshift urine samples were collected. The TEA concentrations were determined by gas chromatography. Tea was measured in air and urine samples from the same shift. Breathing-zone measurements of 19 workers in 3 foundries were included in the study, and stationary and continuous air measurements were also made in the same foundries. Pre- and postshift urine samples were analyzed for their TEA and triethylamine-N-oxide (TEAO) concentrations. The TEA concentration range was 0.3-23 mg/m3 in the breathing zone of the core makers. The mean 8-h time-weighted average exposure levels were 1.3, 4.0, and 13 mg/m3 for the three foundries. Most of the preshift urinary TEA concentrations were under the detection limit, whereas the postshift urinary TEA concentrations ranged between 5.6 and 171 mmol/mol creatinine. The TEAO concentrations were 4-34% (mean 19%) of the summed TEA + TEAO concentrations. The correlation between air and urine measurements was high (r = 0.96, P < 0.001). A TEA air concentration of 4.1 mg/m3 (the current ACGIH 8-h time-weighted average threshold limit value) corresponded to a urinary concentration of 36 mmol/mol creatinine. The TEA exposure levels of foundries and their core makers vary greatly. Stationary air measurements in factories are not sufficient to assess TEA exposure; instead, personal sampling is needed. The biological monitoring of TEA in postshift urine samples provides a practical and accurate method for assessing exposure.

Time-resolved cutaneous absorption and permeation rates of methanol in human volunteers.

This paper reports on an experimental study of dermal exposure to neat methanol in human volunteers for the purposes of estimating percutaneous absorption rates, permeation kinetics, baseline (pre-exposure) levels of methanol in blood, and inter- and intrasubject variability. A total of 12 volunteers (seven men and five women) were exposed to methanol via one hand for durations of 0 to 16 min in a total of 65 sessions, making this the largest controlled study of percutaneous absorption for this common solvent. In each session, 14 blood samples were collected sequentially and analyzed for methanol. These data were used to derive absorption rates and delivery kinetics using a two compartment model that accounts for elimination and pre-exposure levels. The pre-exposure methanol concentration in blood was 1.7 +/- 0.9 mg 1(-1), and subjects had statistically different mean concentrations. The maximum methanol concentration in blood was reached 1.9 +/- 1.0 h after exposure. Delivery rates from skin into blood lagged exposure by 0.5 h, and methanol continued to enter the systemic circulation for 4 h following exposure. While in vitro studies have reported comparable lag times, the prolonged permeation or epidermal reservoir effect for such miscible solvents has not been previously measured. The mean derived absorption rate, 8.1 +/- 3.7 mg cm-2 h-1, is compatible with that found in the other in vivo study of methanol absorption. Both in vivo absorption rate estimates considerably exceed in vitro estimates. The maximum concentration of methanol in blood following an exposure to one hand lasting approximately 20 min is comparable to that reached following inhalational exposures at a methanol concentration of 200 ppm, the threshold limit value-time weighted average (TLV-TWA). While variability in blood concentrations and absorption rates approached a factor of two, differences between individuals were not statistically significant. The derived absorption and permeation rates provide information regarding kinetics and absorbed dose that can help to interpret biological monitoring data and confirm mathematical models of chemical permeation.

Dust Exposures and Ventilation Control in the Crematorium

Abstract An assessment of the potential dust exposure among crematorium workers in the province of Manitoba was conducted. Workers complained of dusty working conditions and possible exposure to radioactive dust. The American Conference of Governmental Industrial Hygienists threshold limit value time-weighted average (TWA) for particulates not otherwise classified is 10 mg/m3 for inhalable particulate mass and 3 mg/m3 respirable particulate mass. Personal inhalable and respirable samples were collected and analyzed according to National Institute for Occupational Safety and Health Methods 0500 and 0600, respectively. All ten crematoria in the province participated in the study. Monitoring was conducted during the processing of bone ash remains (exposure time averaged 23 minutes). Workers' personal exposure for the respirable particulate was minimal, below the lower detection limit (LDL) of 0.3 mg/filter (n = 9). Personal exposures for the inhalable particulate ranged from below the LDL to 12.3 mg/m3 [arithmetic mean (AM) = 4.9, standard deviation (SD) ± 4.2, n = 6; 8-hour TWA = LDL to 0.6 mg/m3]. Poor working conditions in one crematorium resulted in higher personal exposures: respirable particulate was 5.4 mg/m3 (n = 1, TWA = 0.4 mg/m3) and inhalable particulate was 46.1 mg/m3 (n = 1, TWA = 3.6 mg/m3), compared with the majority of crematoria. At another crematorium, monitoring was conducted for four successive remains processed in one workday. Workers' exposure was below the LDL of 0.3 mg/filter (n = 1) for the respirable particulate and was 25.5 mg/m3 (n = 1, TWA = 3.7 mg/m3) for the inhalable particulate. Concentrations for area samples located at each of the processing steps ranged from below the LDL to 16.8 mg/m3 (AM = 2.2, SD ± 4.2, n = 45, TWA = LDL to 0.8 mg/m3). No one processing step generated more dust than another. Engineering controls were installed in two crematoria. Good hygiene practices, respiratory protection, and protective clothing were recommended.

Evaluation of the Adequacy of the Threshold Limit Value for Cyclonite

Abstract Cyclonite (RDX) is an explosive material that is commonly compounded with 2,4,6-trinitrotoluene. The current American Conference of Governmental Industrial Hygienists 8-hour, time-weighted average threshold limit value (TLV) for cyclonite is 1.5 mg/m3 and it contains a “skin” notation. The present study has reviewed the human and animal toxicity literature available for RDX for the purpose of assessing the relative safety of the current RDX standard. Although the only available health study of occupational exposure to RDX finds no evidence of chronic toxicity in areas where the current TLV level was achieved, the evidence for the reported effectiveness of this TLV is of a very limited nature. The animal data are more extensive, and several chronic studies have been completed. When no observed adverse effect levels identified from the chronic animal studies are used to derive a TLV for RDX, and these derivations adopt relatively standard safety factors for this type of animal-to-human dosage extra...

HYDROCARBON EXPOSURES AT PETROLEUM BULK TERMINALS AND AGENCIES

Occupational exposures to the 55 hydrocarbon components of gasoline and petroleum products were measured at the bulk terminals and agencies of six Ontario petroleum companies during the summer of 1986. A total of 82 long-term (full-shift) and 111 short-term personal samples were taken over 3 months. The data, expressed as concentrations in milligrams per cubic meter, were highly variable and appeared to fit the lognormal distribution well. Full-shift exposures of bulk terminal drivers, agency drivers, and plantmen to total hydrocarbons (THC), computed as an n-hexane equivalent, and other hydrocarbon components for which exposure limits exist can be expected to exceed their respective 1986-1987 threshold limit value-time-weighted average (TLV-TWA) no greater than 1% of the time on the basis of the lognormal model. The short-term THC exposures of agency truck drivers can be expected to exceed the 1986-1987 TLV-short-term exposure limits about 7% of the time while top-loading and more than 17% while off-loading. For benzene, the short-term exceedance percentages are 1% and 4% for top- and off-loading operations, respectively. For long-term benzene exposures, up to 69% of the assessments can be expected to exceed the 1990-1991 proposed TLV-TWA of 0.3 mg/m3 (0.1 ppm). The full-shift hydrocarbon exposures of agency drivers were significantly higher than those for bulk terminal drivers. At the bulk terminals, the short-term hydrocarbon exposures during top-loading were significantly higher than during bottom-loading.

Hydrocarbon Exposures at Petroleum Bulk Terminals and Agencies

Occupational exposures to the 55 hydrocarbon components of gasoline and petroleum products were measured at the bulk terminals and agencies of six Ontario petroleum companies during the summer of 1986. A total of 82 long-term (full-shift) and 111 short-term personal samples were taken over 3 months. The data, expressed as concentrations in milligrams per cubic meter, were highly variable and appeared to fit the lognormal distribution well. Full-shift exposures of bulk terminal drivers, agency drivers, and plantmen to total hydrocarbons (THC), computed as an n-hexane equivalent, and other hydrocarbon components for which exposure limits exist can be expected to exceed their respective 1986-1987 threshold limit value-time-weighted average (TLV-TWA) no greater than 1% of the time on the basis of the lognormal model. The short-term THC exposures of agency truck drivers can be expected to exceed the 1986–1987 TLV-short-term exposure limits about 7% of the time while top-loading and more than 17% while off-loading. For benzene, the short-term exceedance percentages are 1% and 4% for top- and off-loading operations, respectively. For long-term benzene exposures, up to 69% of the assessments can be expected to exceed the 1990–1991 proposed TLV-TWA of 0.3 mg/m3 (0.1 ppm). The full-shift hydrocarbon exposures of agency drivers were significantly higher than those for bulk terminal drivers. At the bulk terminals, the short-term hydrocarbon exposures during top-loading were significantly higher than during bottom-loading.

Determination of bromine in air by ion mobility spectrometry

An ion mobility spectrometer (IMS) was used to study the negative ion chemistry of bromine and monitor its concentration in a series of laboratory experiments and in the ambient air of a chemical production facility. Under the conditions of the IMS, three negative ions, Br −, Br 2 − and Br 3 −, were produced from bromine. The relative abundance of Br 3 − increased with the bromine concentration, whereas those of Br − and Br 2 − decreased owing to the ion-molecule reactions they undergo with bromine. The presence of chlorine, other bromides and chlorides did not adversely affect the determination of bromine. In all field measurements, the maximum bromine levels measured were below 30 ppb, well below its 8-h time-weighted average threshold limit value (TWA-TLV) of 100 ppb. The rapid response of the IMS was evident from the effect of changes in wind direction or velocity on the measured concentrations.

Tropospheric Ozone: The Dynamics of Human Exposure

The conditions in the ambient atmosphere conducive to ozone exposure are examined, and placed into a context of the time and locations where individuals would be expected to be affected by high ozone. This is done for both 1 h and 8 h averaging times. Concentrations of ozone in the ambient atmosphere can violate the National Ambient Air Quality Standard (NAAQS) and also the Time Weighted Average-Threshold Limit Value (TWA-TLV) for workers. Exposures that occurred in a 1982 episode associated with a health effects study are described in detail. The effective dose received by a camper at a children's summer camp appeared to be similar to that delivered to volunteers during a controlled human exposure study in which effects on pulmonary function were observed.

The Determination of the Odor Threshold of Telone® II Soil Fumigant by a New Method

Abstract A method has been developed for the determination of the olfactory threshold of vapors and gases. It involves the dilution of a concentrated vapor or gas by a metering pump into an odorfree stream of air and an odor-free sampling system. Its advantage over other methods is the speed and accuracy with which odor thresholds can be determined. This method has been used to determine the odor of Telone® II Soil Fumigant in air. In a population of 22 persons, the concentration at which odor was detected was 4.4 ± 3.1 ppm (mean ± S.D.). This level is slightly above the current threshold limit value time-weighted average of 1.0 ppm but below the short-term exposure limit of 10 ppm.

Detection of cadmium, lead and zinc in aerosols by laser-induced breakdown spectrometry

The repetitive breakdown spark from an Nd: YAG laser was used to generate analytical emission spectra of cadmium, lead and zinc in aerosols. The laser was typically operated at a pulse rate of 10 Hz, with an energy of 100 mJ per pulse and a pulse width of approximately 15 ns. Samples were generated in aerosol form by a nebuliser-heat chamber arrangement. The detection apparatus consisted of a monochromator, photomultiplier tube and boxcar averager. The last component provided amplification, averaging and time resolution. Detection limits for cadmium, lead and zinc in aerosols were 0.019, 0.21 and 0.24 µg g–1, respectively, at a signal to noise ratio of 3. The detection limits for cadmium and zinc were well below the threshold limit value-time weighted average (TLV-TWA) and threshold limit value-short-term exposure limit (TLV-STEL) limits for these two metals. Calibration graphs covering two orders of magnitude were generated. The excitation temperature of the plasma was measured from 20 to 40 µs after plasma initiation using the two-line Boltzman method, and was found to decrease from 6500 K at 20 µs to 5150 K at 40 µs. The effects of chemical form and sodium on the spectroscopic signals were investigated.