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Observed versus predicted carboxyhemoglobin levels in cellulose triacetate workers exposed to methylene chloride.

BACKGROUND: Occupational exposure to methylene chloride, together with carboxyhemoglobin concentrations, has not been studied previously. METHODS: Carboxyhemoglobin levels were measured in non-smoking employees exposed to varying concentrations of methylene chloride during the manufacture of cellulose triacetate fibers. The observed carboxyhemoglobin levels were compared to predicted concentrations using a pharmacokinetic model. RESULTS: The presence of carboxyhemoglobin in non-smokers exposed to methylene chloride results primarily from the metabolism of methylene chloride in the liver and exhibits a linear dose-response relationship. The observed levels of carboxyhemoglobin in non-smokers at the end of an 8-hour shift depend upon exposures to methylene chloride that day but are independent of occupational exposures on previous days. The observed daily concentrations of carboxyhemoglobin are consistent with predicted concentrations using a pharmacokinetic model. While varying exposure patterns were shown to change the rate of metabolite formation at the end of shift, these same exposure patterns had almost no effect on the total amount of carbon monoxide in the blood. CONCLUSION: While the present study addresses the relationship between methylene chloride, carbon monoxide, carboxyhemoglobin and ischemic heart disease, it does not address the issue of tumorigenicity, which is also the basis for the current U.S. Occupational Health and Safety workplace exposure limit of 25 ppm. This study provides support for the conclusion that the current American Conference of Governmental Industrial Hygienists 8-hour Threshold Limit Value of 50 ppm adequately protects human health with regard to ischemic heart disease and carboxyhemoglobin formation among non-smokers.

Carbon Monoxide↗

Accelerated loss of FEV- in polyurethane production workers: a four-year prospective study.

A four-year longitudinal study of ventilatory function in polyurethane-foam production workers exposed to toluene diisocyanate (TDI) revealed a dose-response relationship between average exposure to TDI and change in forced expiratory volume per second (FEV-1). Workers with mean exposure in excess of 0.0035 ppm showed a greater rate of decline of FEV-1 over the four-year period than that expected from aging. Factors other than TDI exposure (sex, smoking history, history of atopy) do not account for the loss. The current threshold limit value (TLV) for exposure to TDI in industry (0.02 ppm) does not protect workers from accelerated impairment of ventilatory capacity.

Cyanates↗

A cross-sectional survey of kidney function in refinery employees.

We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.

Adult↗

Sister chromatid exchanges and DNA repair capability in sanitary workers exposed to ethylene oxide: evaluation of the dose-effect relationship.

Determination of ethylene oxide (EtO) in the working environment and induction of sister chromatid exchanges (SCE) and unscheduled DNA synthesis (UDS) in peripheral lymphocytes of 10 exposed sanitary workers and 10 control subjects matched for sex, age, and smoking habits are reported. The relationship between the external dose of EtO and the frequency of SCE was determined in the above group and in a group of 41 sanitary workers previously studied. The 10 newly examined workers were exposed to EtO concentrations (1.84 ppm as time-weighted average) intermediate between the high (10.7 ppm) and low (0.35 ppm) levels of exposure of the two previously examined groups (19 and 22 workers, respectively). A statistically significant (p less than 0.002) increase of SCE frequency was observed between the present control and exposed groups. The inducibility of unscheduled DNA synthesis by gamma rays was lower in the lymphocytes of the exposed workers than in controls, but the difference was not statistically significant. A significant relationship between the frequency of SCE and the level of EtO exposure for the three exposed groups was demonstrated by two different statistical methods. It is suggested that the present Italian threshold limit value for EtO (3 ppm) may not protect the exposed workers against possible genotoxic effects and that even a chronic exposure to 1 ppm may not be devoid of genotoxic risk.

Chromosome Aberrations↗

Fluoride in workplace air and in urine of workers concentrating fluorspar.

The urinary fluoride concentrations of workers exposed to calcium fluoride (CaF2) during fluorspar processing were measured. Personal dust measurement showed that the mean occupational exposure to fluoride for 12 workers in the most dusty environment was 24.3 mg/m3, which is 9.7 times the threshold limit value (TLV) of 2.5 mg/m3. Exposure was below the TLV for the remaining 23 workers. Urinary fluoride concentrations were measured pre- and postshift. The heavily exposed workers had a mean preshift concentration of 3.3 mg/liter (range 1.4-8.5 mg/liter), only slightly higher than the mean of 2.8 mg/liter (range 1.3-4.2 mg/liter) in the workers with fluoride exposure below the TLV. Four of the preshift concentrations exceeded the recommended upper limit of 4 mg/liter. The mean postshift concentration for workers exposed above the TLV was 4.4 mg/liter (range 2.4-7.1 mg/liter) and the difference between pre- and postshift concentrations was significant (p less than 0.05). Only one urinary concentration exceeded the recommended upper limit of 7 mg/liter. There was poor correlation between intensity of environmental exposure to fluorspar and postshift fluoride concentration in the urine. Eighteen workers provided a urine sample 7-14 hr after the end of a shift. The mean fluoride concentration was 4.7 mg/liter (range 2.4-11.7 mg/liter), which exceeded their postshift concentration by 0.2 mg/liter. These results indicate that the low aqueous solubility of fluorspar reduced the biologic availability of the fluoride ion but that this did not prevent excessive fluoride absorption in some workers.

Air Pollutants, Occupational↗

Biological monitoring of nitrous oxide exposure in surgical areas.

Exposure to nitrous oxide in surgical theaters was evaluated for duration, numbers, and types of surgical procedures. The concentration of the gas in the air was 92-444 ppm. Before and after the surgical sessions, samples of urine and expired air were collected from surgical theater personnel for gas determination. Nitrous oxide concentrations in urine and in expired air showed a good correlation with gas concentration in the air (r = 0.760 and r = 0.921, respectively). Moreover, a good correlation (r = 0.823) between gas concentration in urine and that in expired air was also found. A biological threshold limit value (TLV) of 20.6 micrograms/liter for urine and of 29.6 ppm for expired air was calculated, based on the limit of 50 ppm in the air proposed by the American Conference of Governmental Industrial Hygienists (ACGIH). Other biological TLVs corresponding to higher proposed limits (200 and 500 ppm) were also calculated.

Adult↗

Solvent-associated decrements in olfactory function in paint manufacturing workers.

To assess the effects of low-level organic solvent exposure on olfactory function, a cross-sectional study in paint manufacturing workers was undertaken. Workers in two paint manufacturing facilities (N = 187) were tested using the University of Pennsylvania Smell Identification Test (UPSIT), a standardized, quantitative test of olfactory function. Industrial hygiene air samples over the past 13-15 years revealed that average solvent exposures in these plants were 2-40% of the existing threshold limit values for the three chemicals measured. Stratification by smoking status revealed evidence of dose-related decrements in olfactory function (p = .01) only in non-smokers. Furthermore, those nonsmoking workers in the highest exposure category had UPSIT scores below the fifth percentile for their age. These results suggest that solvents may cause nervous system dysfunction at lower levels than previously suspected, and that the olfactory system may be a critical target organ for the neurotoxic effects of solvents and other chemicals.

Adult↗

Implications of OSHA's reliance on TLVs in developing the air contaminants standard.

This paper evaluates the decision by the Occupational Safety and Health Administration (OSHA) to base its Air Contaminants Standard on the threshold limit values (TLVs) of the American Conference of Governmental Industrial Hygienists. Contrary to the claim made by OSHA in promulgating the standard, the TLV list was not the sole available basis for a generic standard covering toxic air contaminants. The National Institute for Occupational Safety and Health (NIOSH) presented data indicating that the TLVs were insufficiently protective for 98 substances. NIOSH Recommended Exposure Limits (RELs) were available for 59 of these substances. The ratio of PEL to REL ranged up to 1,000, with a median of 2.5 and a mean of 71.4. OSHA excluded 42 substances from the standard altogether despite the availability of NIOSH RELs, solely because no TLV had been established.

Air Pollutants, Occupational↗

Respiratory symptoms, ventilatory impairment, and bronchial reactivity in oil mist-exposed automobile workers.

Studies concerning the respiratory effects of oil mists are sparse and contradictory. The aim of this study was to determine the respective effects of occupational exposure to straight cutting oils and soluble mineral oils on the prevalence of respiratory symptoms, ventilatory impairment, and bronchial reactivity. The population study consisted of 308 male workers of a large French car-making plant, including 40 subjects chronically exposed to straight cutting oils (group S), 51 subjects chronically exposed to soluble mineral oils (group E), 139 subjects with chronic dual exposure to straight cutting oils and soluble mineral oils (group D), and 78 unexposed assembly workers used as a control group (group C). Worker evaluation included a standardized questionnaire, measurement of pulmonary function, and a methacholine challenge. Oil mist concentration at the work place was determined by gravimetric analysis. The arithmetic mean concentration was 2.6 +/- 1.8 mg/m3. The geometric mean concentration was 2.2 +/- 1.9 mg/m3. The prevalence of respiratory symptoms did not differ significantly among the four groups. However, the subjects exposed to straight cutting oils (group S + group D) had a significantly higher prevalence of chronic cough and/or phlegm than the others (group E + group O): 25.7% vs. 16.3% (p = 0.048). Furthermore, the prevalence of cough and/or phlegm increased significantly (p = 0.03) with increasing duration of exposure to straight cutting oils after adjustment on smoking categories. Lung function tests did not differ significantly among the four groups but we observed a significant decrease of forced expiratory volume in 1 sec (FEV1), forced expiratory flow during the middle half of forced vital capacity (FEF25-75), and maximal flow rate at 50% and 25% of exhaled forced vital capacity (V50 and V25) according to duration of exposure among smokers exposed to straight cutting oils, suggesting a synergistic effect of tobacco and insoluble oils. No effect of exposure to mineral oils on bronchial reactivity was demonstrated. It is concluded that despite low levels of pollution by oil mists, the present study has shown tenuous adverse chronic effects of straight cutting oils on respiratory symptoms and lung function. However, no adverse effect of soluble mineral oils was demonstrated. These results suggest that threshold limit values for mineral oils should be reassessed.

Adult↗

Estimation of risk of developing bladder cancer among workers exposed to coal tar pitch volatiles in the primary aluminum industry.

To confirm the relationship between exposure to coal tar pitch volatiles and bladder cancer among primary aluminum production workers, we carried out a case-control study among blue-collar workers who had worked more than 1 year between 1950-1979 in a major plant using mostly the Soderberg process in the Province of Québec. Cases of bladder cancer (ICD code 188) diagnosed between 1970-1979 (n = 69) were mostly included in a previously reported study. To these were added cases diagnosed between 1980-1988 (n = 69). Each case was matched to three controls on date of birth, date of hiring, and length of service at the company. Smoking habits were assessed from the medical records at the company. Benzene-soluble matter (BSM) and benzo(a)pyrene (BaP) were used as indicators of environmental exposure to coal tar pitch volatiles in the workplace. The estimated risk for current smokers was 2.63 (95% C.I. 1.29-5.37). Estimates of risk by occupational exposure were adjusted for smoking. Men who had worked in the Soderberg potrooms were at higher risk of developing the disease, the risk increasing with the time spent in these departments. Similarly, a strong association between risk and cumulative exposure to BSM or to BaP was observed. The risks associated with cumulative exposure to BSM (mg/m3-years) and to BaP (microgram/m3-years) were described with mathematical models. Using a linear model (1 + bx) and lagging 10 years before the diagnosis, BaP cumulative exposure was a better indicator of risk than BSM cumulative exposure. The risk for each year of exposure to BaP at a concentration of 1 microgram/m3 increased by 1.7% (0.8%-3.2%). Using the same model for BSM, a worker exposed to the current threshold limit value of 0.2 mg/m3 for 40 years will sustain a risk of 2.22 (1.56-3.48). Comparison of risks according to different periods of diagnosis (1970-1979 vs. 1980-1988) did not reveal any significant temporal changes on risk estimates.

Air Pollutants, Occupational↗

Neurobehavioral effects of acute and chronic mixed-solvent exposure in the screen printing industry.

This 2-year prospective study examined the neurobehavioral effects of acute and chronic exposure to mixed solvents in workers in a screen printing business. A total of 30 subjects participated in the study in two field testings over a 12 month period. Each subject completed a detailed medical and occupational questionnaire, had a neurological examination, and underwent a battery of neuropsychological tests. Industrial hygiene investigation identified the following chemical exposures as present: toluene, methyl ethyl ketone, mineral spirits, beta-ether, methylene chloride, and acetic acid. Different departments and jobs had varying degrees of exposure to these chemicals, the highest exposures being in the ink mix area and the screen washroom area. However, all exposure levels were below recommended threshold limit values. Persons categorized as having higher acute exposure demonstrated significantly impaired test performance on tasks involving manual dexterity, visual memory, and mood. Those with higher chronic exposure demonstrated significantly poorer performance on visual memory tasks and mood. Results suggest that the mixed solvents used in the screen printing industry have an effect on central nervous system functioning in the absence of obvious clinical disease.

Adult↗

Rapid determination of O- and P-cresol isomers in urine from workers exposed to toluene by high-performance liquid chromatography using a graphitized carbon column.

A simple and rapid procedure is described that permits the simultaneous determination of o- and p-cresol in urine of workers of other individuals exposed to toluene. The urine samples are enzymatically hydrolysed and analysed by high-performance liquid-chromatography with a detection limit of 0.2 mg/L, one fifth of the biological threshold limit value for o-cresol (1 mg/g), a specific marker of toluene exposure. A graphitized carbon column Hybercarb-S, that exhibits an excellent selectivity for aromatic positional isomers, was used with 1% phosphoric acid-acetonitrile (70:30, v/v) as mobile phase and a detection wavelength of 271 nm. The overall accuracy for o-cresol determination was 4.5% at 5 mg/L and 8% at 0.5 mg/L. The cresol isomers were sufficiently resolved from endogenous materials to avoid the need for any extraction step, and the method appears suitable for monitoring workers accurately under the permissible level of exposure for occupational medicine purpose.

Chromatography, High Pressure Liquid↗

Organic solvents and chronic glomerulonephritis: a cross-sectional study with negative findings for aliphatic and alicyclic C5-C7 hydrocarbons.

Proteinuria, albuminuria, urinary beta-glucuronidase and serum creatinine were estimated in 182 workers exposed to organic solvents in four shoe factories, as well as 30 workers with past exposure and 80 control subjects. Ambient air concentrations at each workplace were also measured. In most of these samples, the concentration of organic solvents exceeded the ACGIH recommended threshold limit value for the mixture. Total protein excretion was significantly elevated in exposed workers, although none of the workers had abnormal albuminuria or serum creatinine. Four had increased lysozymuria. There was also a simultaneous elevation of beta-glucuronidase. These findings suggest that a mild and presumably reversible tubular lesion, but not glomerular damage, may occur in workers occupationally exposed to C5-C7 hydrocarbon mixtures.

Adult↗

Effects of formaldehyde and acetaldehyde inhalation on rat pulmonary mechanics.

Two groups of 12 male Wistar rats received either 243 ppm of acetaldehyde or 5.7 ppm of formaldehyde for 8 h a day, 5 days a week during 5 weeks. These levels represent three times the threshold limit values (TLV) for these substances in Brazilian legislation. The animals were evaluated by pulmonary function tests before and after exposure to the pollutants. The data obtained from these rats were compared with those of 12 controls, housed in identical conditions for the same length of time but breathing normal air. The results showed an increase of the functional residual capacity, residual volume, total lung capacity and respiratory frequency in the rats exposed to acetaldehyde atmosphere. The animals exposed to formaldehyde did not present pulmonary function alterations when compared with the controls. The damage caused by acetaldehyde to the peripheral regions of the lung parenchyma, affecting small airways or altering pulmonary elastic properties, is discussed. It is suggested that the Brazilian TLV for acetaldehyde (78 ppm) is not as safe as that for formaldehyde (1.6 ppm).

Acetaldehyde↗

Two-generation reproduction study on commercial hexane solvent.

The reproductive effects of inhalation exposure to commercial hexane vapors were evaluated in Sprague-Dawley rats. Males and females were exposed to commercial hexane vapor at target concentrations of 0, 900, 3000 or 9000 ppm for 6 h a day, 5 or 7 days a week, over two generations. In addition to pre-breed exposures of 10 weeks' duration, exposures continued through mating, gestation and lactation. At both the F0 breed to produce F1 litters and the F1 breed to produce F2 litters, reproductive parameters were unaffected by commercial hexane exposure. The mating, fertility and gestational indices, as well as litter size and postnatal survival, were not significantly different between exposure groups. However, reductions in body weight and body weight gain were observed in both F1 and F2 litters exposed to 9000 ppm. Effects on body weight were not observed in offspring exposed to the two lower concentrations of commercial hexane. Histopathological examination of selected tissues revealed hyaline droplet nephropathy in adult F0 and F1 males exposed to 9000 ppm. This finding was anticipated and is not believed to be relevant for the assessment of human health effects. No other treatment-related histopathological lesions were observed. Thus, exposure of rats to commercial hexane for two generations resulted in reduced body weight gains at 9000 ppm but no adverse effects on reproduction. These findings suggest that occupational exposure to commercial hexane vapors at currently recommended threshold limit value concentrations (i.e. TLV for n-hexane is 50 ppm and TLV for other hexane isomers is 500 ppm) should not pose a reproductive hazard.

Administration, Inhalation↗

Pulmonary absorption and excretion of compounds in the gas phase: theoretical pharmacokinetic and toxicokinetic analysis.

Kinetic equations were derived that describe the plasma concentration of an inhaled compound during and following single or repeated regular and irregular pulmonary exposures. The equations are based on a diffusional type of input function and assume a linear disposition with a biexponential unit-impulse response. The use of linear system analysis avoids the complexity of modeling the disposition processes; yet, the effect of these processes is still accounted for mathematically. The approach, therefore, appears to be more general and rational than approaches based on linear compartmental modeling. The ways in which the kinetic equations can be readily applied in pharmacokinetic or toxicokinetic analyses to obtain valuable parameters that enable kinetic predictions of the cumulation during prolonged exposure are discussed. The toxicokinetic problem of comparing the effect of different work schedules in occupational environments with air contaminants is discussed. Formulas derived from considerations of the blood plasma kinetics are presented for the calculation of an adjustment factor for the adjustment of the contaminant threshold limit value for abnormal work weeks. The use of these formulas appears to be more rational than that of similar formulas that have been proposed.

Absorption↗

Human experimental MIBK exposure: effects on heart rate, performance, and symptoms.

Heart rate, performance, and symptoms were studied in six female and six male volunteers, aged 19 to 47 years, during experimental 2-hr exposures to 10 and to 200 mg/m3 of methyl isobutyl ketone (MIBK). No effects from exposure on performance of a reaction time task or an arithmetic test could be demonstrated, and no consistent effects on heart rate were found. Subjects reported significantly more symptoms from the central nervous system, e.g., fatigue, due to the exposure. There was also an indication of an increase in ratings of irritation to the airways. A reduction of the threshold limit value (TLV) of 205 mg/m3 for MIBK exposure presently indicated by the American Conference of Governmental Industrial Hygienists, is therefore recommended.

Adult↗

A cross-sectional survey of neurobehavioral effects of chronic solvent exposure on workers in a paint manufacturing plant.

Neurobehavioral impairments in 84 workers with long-term exposure to organic solvents in a paint manufacturing plant were examined cross sectionally. The World Health Organization (WHO) Neurobehavioral Core Test Battery, the NES-2 computerized battery, and four additional South African tests were used. Exposure to solvents was determined by using company industrial hygiene data as well as from an industrial hygiene survey of current total solvent levels in air. Indexes for cumulative exposure and average lifetime intensity of exposure were calculated for groups of homogeneously exposed workers in each department. Exposure levels were below the AGGIH threshold limit values. Multiple linear regression revealed that education level, age, and alcohol consumption were strong predictors for several neurobehavioral test scores. After adjusting for potential confounding from this source, average lifetime intensity of solvent exposure was the most significant predictor of the NES-2 Continuous performance test (measuring sustained visual attention) score of the WHO Digit span backward test score (measuring attention span and double tracking). Pursuit aiming (measuring fine visuomotor tracking speed) was significantly associated with the cumulative exposure index, possibly indicating early neurotoxic effects.

Central Nervous System↗