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Occupational chronic exposure to organic solvents XVII. Ambient and biological monitoring of workers exposed to xylenes.

OBJECTIVE: Ambient-air and biological monitoring of occupational xylene exposure were carried out on 2 groups of workers (13 and 10 men, respectively) exposed to a mixture of xylenes during the production of paints or during spraying. METHODS: Personal ambient-air monitoring was performed for one complete work shift. Blood and urine samples were collected directly at the end of the shift. Biological monitoring was based on the determination of the concentration of xylenes in blood and on the quantification of the sum of the three methylhippuric acids in urine. RESULTS: Average xylene ambient-air concentrations were 29 ppm (production) and 8 ppm (spraying), ranging from 5 to 58 ppm and from 3 to 21 ppm, respectively. The concentrations of xylenes in blood ranged from 63 to 715 microg/l and from 49 to 308 microg/l, with average values being 380 and 130 microg/l, respectively. Accordingly, the workers engaged in paint production also excreted more methylhippuric acids in their urine (average 1221 mg/l, range 194 2333 mg/l) than did the sprayers (average 485 mg/l, range 65-1633 mg/l). DISCUSSION: Our results as well as a literature review indicate that occupational xylene exposure on average barely exceeds the threshold limit value of 100 ppm as proposed by both American and German institutions. Biological monitoring based on the determination of xylenes in blood and of methylhippuric acids in urine provides sufficient sensitivity and specificity for occupational health surveillance. The results also confirm the current limit values (BAT values) proposed by the Deutsche Forschungsgemeinschaft for xylenes in blood (1500 microg/l) and methylhippuric acids in urine (2000 mg/l).

Adult↗

Lung function, biological monitoring, and biological effect monitoring of gemstone cutters exposed to beryls.

OBJECTIVES: Gemstone cutters are potentially exposed to various carcinogenic and fibrogenic metals such as chromium, nickel, aluminium, and beryllium, as well as to lead. Increased beryllium concentrations had been reported in the air of workplaces of beryl cutters in Idar-Oberstein, Germany. The aim of the survey was to study the excretion of beryllium in cutters and grinders with occupational exposure to beryls--for example, aquamarines and emeralds--to examine the prevalence of beryllium sensitisation with the beryllium lymphocyte transformation test (BeLT), to examine the prevalence of lung disease induced by beryllium, to describe the internal load of the respective metals relative to work process, and to screen for genotoxic effects in this particular profession. METHODS: In a cross sectional investigation, 57 out of 100 gemstone cutters working in 12 factories in Idar-Oberstein with occupational exposure to beryls underwent medical examinations, a chest radiograph, lung function testing (spirometry, airway resistance with the interrupter technique), and biological monitoring, including measurements of aluminium, chromium, and nickel in urine as well as lead in blood. Beryllium in urine was measured with a newly developed direct electrothermal atomic absorption spectroscopy technique with a measurement limit of 0.06 microgram/l. Also, cytogenetic tests (rates of micronuclei and sister chromatid exchange), and a BeLT were performed. Airborne concentrations of beryllium were measured in three factories. As no adequate local control group was available, the cutters were categorised into those with an exposure to beryls of > 4 hours/week (group A) and < or = 4 hours/week (group B). RESULTS: Clinical, radiological, or spirometric abnormalities indicating pneumoconiosis were detected in none of the gemstone cutters. Metal concentrations in biological material were far below the respective biological limit values, and beryllium in urine was only measurable in subjects of group A. Cytogenetic investigations showed normal values which were independent of the duration of beryllium exposure. In one subject, the BeLT was positive. Beryllium stimulation indices were significantly higher in subjects with detectable beryllium in the urine than in those with beryllium concentrations below the detection limit (p < 0.05). In one factory, two out of four measurements of airborne beryllium concentrations were well above the German threshold limit value of 2 micrograms/m3 (twofold and 10-fold), and all gemstone cutters working in this factory had measurable beryllium concentrations in urine. CONCLUSION: No adverse clinical health effects were found in this cross sectional investigation of gemstone cutters working with beryls. However, an improvement in workplace hygiene is recommended, accompanied by biological monitoring of beryllium in urine.

Adult↗

"Dynamic" biological exposure indexes for n-hexane and 2,5-hexanedione, suggested by a physiologically based pharmacokinetic model.

Biological exposure index (BEI) of n-hexane was studied for accuracy using a physiologically based pharmacokinetic (PB-PK) model. The kinetics of n-hexane in alveolar air, blood, urine, and other tissues were simulated for different values of alveolar ventilations and also for constant and variable exposures. The kinetics of 2,5-hexanedione, the toxic n-hexane metabolite, were also simulated. The ranges of n-hexane concentrations in biological media and the urinary concentrations of 2,5-hexanedione are discussed in connection with a mean n-hexane exposure of 180 mg/m3 (50 ppm) (threshold limit value [TLV] suggested by American Conference of Governmental Industrial Hygienists [ACGIH] for 1988-89). The experimental and field data as well as those predicted by simulation with the PB-PK model were comparable. The physiological-pharmacokinetic simulations are used to propose the "dynamic" BEIs of n-hexane and 2,5-hexanedione. The use of simulation with PB-PK models enables a better understanding of the limits, advantages, and issues associated with biological monitoring of exposures to industrial solvents.

Hexanes↗

Urinary fluoride monitoring of industrial hydrofluoric acid exposure.

Preworkshift and postworkshift urinary fluoride concentrations were measured in 142 hydrofluoric acid (HF) workers and 82 unexposed workers aged 18 to 59. Postshift urinary fluoride concentration in HF workers was significantly higher than that in preshift or control workers. A linear relationship was observed between the mean values in urinary fluoride concentration and the HF concentration in the air. The mean urinary fluoride concentration of 4 ppm and its lower fiducial limit (95%, P = 0.05) of 2 ppm (specific gravity 1.024) were estimated corresponding to the atmospheric HF concentration of 3 ppm, which is the maximal allowable concentration recommended by the Japanese Association of Industrial Health and also the threshold limit value suggested by the American Conference of Governmental Industrial Hygienists. The results suggest that exposure to HF can be monitored by determining the urinary fluoride concentration.

Adolescent↗

Work related impairment of nasal function in Swedish woodwork teachers.

OBJECTIVE: To study the relation between exposure and nasal function in woodwork teachers. METHODS: 39 selected woodwork teachers employed full time and 32 control subjects (other school personnel) were examined at the beginning and at the end of a working week with symptom rating, nose and throat inspection, rhinomanometry, nasal mucociliary clearance test, and a smell identification test. During one working day of the same week climate, dust and terpene concentrations were measured in all 39 schools. RESULTS: The ventilation rate was highest in rooms with mechanical ventilation. Range of total dust (personally sampled) was 0.12-1.18 mg/m3, respirable dust 0.02-0.21 mg/m3, and terpenes (area sampled) 0.02-6.8 mg/m3. In contrast to the control subjects, the woodwork teachers had more nasal symptoms on the Thursday afternoon than on the Monday morning, especially those working in rooms without mechanical ventilation. Their mucociliary clearance worsened during the week (mean increase 4 min, P < 0.001). A small impairment of olfactory function was also found, but their rhinomanometric values did not change significantly. Nasal symptoms correlated weakly with the percentage of respirable dust in the total dust. Otherwise there were no significant dose-effect relations between measured dust or terpene concentrations and nasal tests. CONCLUSIONS: The woodwork teachers had mainly reversible nasal complaints, impaired nasal mucociliary clearance and olfactory function related to the work environment, with dust concentrations below the Swedish threshold limit value of 2 mg/m3.

Adult↗

Selective vulnerability of dopaminergic systems to industrial chemicals: risk assessment of related neuroendocrine changes.

Increased serum prolactin (PRL) is a common finding among subjects exposed to styrene, perchloroethylene, lead (Pb), and manganese (Mn) at levels below the current threshold limit values. On a group basis, abnormally high basal PRL shows a dose-related distribution among workers exposed to styrene, Pb, and Mn. On the basis of dose-response relationships, the benchmark doses (BMD) for styrene metabolites in urine, lead in blood (Pb-B), and Mn in urine (Mn-U), are 4 mg/g creatinine, 112 micrograms/L, and 0.3 microgram/L, respectively. Noteworthy, the BMD for Mn-U and Pb-B is well below the upper reference limit. A shift in the distribution but not in the prevalence of abnormally high values of serum PRL was observed among perchloroethylene-exposed dry cleaners, which makes interpretation in terms of risk difficult. The measurement of PRL thus provides opportunities for early identification of excess exposure to neurotoxic chemicals affecting dopaminergic control of pituitary secretion. For styrene, Pb, and Mn the BMD provides an objective and statistically determined threshold, which seems to be in good agreement with the estimated no-observed-adverse-effect-level (NOAEL). The NOAEL, however, is based on traditional approaches that require the application of uncertainty factors, e.g., a default factor of 10 when extrapolating the NOAEL from the lowest-observed-adverse-effect-level (LOAEL). Due to its sensitivity to a number of potential confounders, caution must be exercised when using PRL as a screening test at the individual level. Also, age and sex dependent variations in susceptibility may hamper extrapolations from the occupational settings to the general population.

Biomarkers↗

Pneumoconiosis and exposures of dental laboratory technicians.

One hundred and seventy-eight dental laboratory technicians and 69 non-exposed controls participated in an epidemiological respiratory study. Eight technicians who had a mean of 28 years' grinding nonprecious metal alloys were diagnosed as having a simple pneumoconiosis by chest radiograph. Mean values for per cent predicted FVC and FEV1 were reduced among male nonsmoker technicians compared to male nonsmoker controls; after controlling for age, there was also a reduction in spirometry with increasing work-years. An industrial hygiene survey was conducted in 13 laboratories randomly selected from 42 laboratories stratified by size and type of operation in the Salt Lake City, Utah metropolitan area. Personal exposures to beryllium and cobalt exceeded the Threshold Limit Values (TLVs) in one laboratory. Occupational exposures in dental laboratories need to be controlled to prevent beryllium-related lung disorders as well as simple pneumoconiosis.

Adult↗

Rationale for a personal monitor for heat strain.

Worker heat-stress exposures can be controlled for short periods above the threshold limit value (TLV) by self-assessment, if the worker can avoid overexposure based on excessive heart rate and/or excessive core temperature. A socially acceptable surrogate for core temperature and a measure of heart rate are objective measures that can increase the reliability of the self-assessment decision. This article describes a surface-mounted temperature sensor developed to indicate when rectal temperature reaches a safe limit. Protective criteria were established for temperature sensor alert limits. A fixed threshold for heart rate may cause premature alerts during bursts of activity and miss lower, but sustained, heart rates that represent significant physiological strain. For these reasons, heart rate criteria based on seven moving-time averages also were developed. The criteria are based on a relationship between heart rate and endurance time. The temperature sensor and heart rate criteria form the basis of a real-time personal monitor for heat strain.

Body Temperature↗

Rat lung metallothionein and heme oxygenase gene expression following ozone and zinc oxide exposure.

We have conducted exposures in rats to determine pulmonary responses following inhalation of two common components of welding fumes, zinc oxide and ozone. To examine their effects on target-inducible gene expression, we measured mRNA levels of two metal-responsive genes, metallothionein (MT) and heme oxygenase (HO), in lung tissue by RNA slot-blot analysis. A 3-hr exposure to ZnO fume via a combustion furnace caused a substantial elevation in lung MT mRNA at all concentrations tested. Exposures to 5 and 2.5 mg/m3 ZnO resulted in peak 8-fold increases in MT mRNA levels (compared to air-exposed control animal values) immediately after exposure, while 1 mg/m3 ZnO exposure caused a 3.5-fold elevation in MT mRNA. These levels returned to approximate control gene expression values 24 hr after exposure. In addition, ZnO exposure caused an immediate elevation in lung HO gene expression levels, with 8-, 11-, and 5-fold increases observed after the same ZnO exposure levels (p < 0.05). Like MT gene induction, HO mRNA values returned to approximate control levels 24 hr after exposure. In striking contrast to the induction of MT and HO gene expression after ZnO exposures, there was no elevation in gene expression following a 6-hr exposure to 0.5 and 1 ppm ozone, even when lungs were examined as late as 72 hr after exposure. Our results demonstrate the induction of target gene expression following the inhalation of ZnO at concentrations equal to, and below, the current recommended threshold limit value of 5 mg/m3 ZnO. Furthermore, the lack of effect of ozone exposure on MT and HO gene expression suggests no involvement of these genes in the acute respiratory response to this oxidant compound.

Administration, Inhalation↗

A Model to Estimate the Delivered Doses of Substances in Liquid and Gaseous Phases.

A conceptual model is presented for assessing the dose of a chemical substance delivered to individual lung cells when exposure can occur through inhalation of the substance as either a gas or an aerosol of droplets. Assuming a threshold value for the concentration of a toxic species in a single cell, the model shows that the physical state of the substance may affect its biologic activity. Exposure to aerosol droplets of an irritating or reactive substance will deliver much higher surface concentrations to single cells than will a similar exposure to a gas. Under certain conditions, the surface concentration can be between 100 and 10&sup10; times higher when the exposure involves an aerosol. Indirect support for the model is found in the observations that threshold limit values for aerosols are generally lower than those for gases.

Journal Article↗

[Reference values necessary for the interpretation of biological surveillance].

The paper presents an integrated system if guide values, represented by reference values, action levels, limit values, theoretically able to cover the interpretation of all the data from biological monitoring. This practice, requires in fact accurate values to which refer for demonstrating exposures to xenobiotics, and their early health effect. The procedures to select subjects, to control pre analytical and analytical factors, to apply correct statistical methods for establishing accurate reference values are recalled, and the relationship between the different guide values discussed.

Environmental Monitoring↗

Influence on vision of extremely low frequence electromagnetic fields. Industrial measurements, magnetophosphene studies volunteers and intraretinal studies in animals.

The strong electric currents used for heating purposes in welding and steel industries set up related magnetic fields (generally 0.1--10 mT and 50 Hz). Such fields 10--50 Hz, 0--40 mT) were used to induce visual light phenomena, magnetophosphenes. Threshold values for magnetophosphenes were determined as a function of magnetic field frequency as well as colour and intensity of the background illumination. A typical sensitivity maximum was found at 20--25 Hz. Differences between volunteers with normal colour vision and colour defective ones were observed. The frog retina was exposed to the same type of fields. Retinal activity, induced by the fields, was registered from the ganglion cell layer by means of microelectrode technique. The results indicate that magnetophosphenes are generated in the retina and in the same channels that are normally propagating signals induced by light of different qualities. The findings may be of guidance when formulating threshold limit values for extremely low frequency electromagnetic fields in industry.

Animals↗

Serum fluoride as an indicator of occupational hydrofluoric acid exposure.

To define the relationship between ionic fluoride concentration in the serum of workers and the amount of hydrofluoric acid (HF) in the work environment, pre-and postshift serum and urine samples of 142 HF workers and 270 unexposed workers were examined. The maximum and minimum concentrations of HF in the air in each workshop varied from the mean by less than 30%. The preexposure levels of serum and urinary fluoride in HF workers were higher (P < 0.001) than the control values. This suggests that fluoride excretion from the body continues for at least 12h. The postshift serum and urinary fluoride concentrations of these workers were significantly higher (P < 0.001) than the preshift concentrations. A good correlation (r = 0.64) was obtained between postshift serum fluoride and postshift urine fluoride. There was a linear relationship between mean serum fluoride concentration and HF concentration in the workshop. A mean fluoride concentration of 82.3 micrograms/l with a lower fiducial limit (95%, P = 0.05) of 57.9 micrograms/l was estimated to correspond to an atmospheric HF concentration of 3 ppm. This is the maximum allowable environmental concentration recommended by the Japanese Association of Industrial Health, and it is also the threshold limit value suggested by the American Conference of Governmental Industrial Hygienists. The results demonstrate that exposure to HF can be monitored by determining the serum fluoride concentration.

Adolescent↗

Proposal for single and mixture biological exposure limits for sevoflurane and nitrous oxide at low occupational exposure levels.

OBJECTIVES: Assessment of individual exposures to sevoflurane plus nitrous oxide (N(2)O) by biological monitoring of unmodified analytes in post-shift urine of exposed personnel. METHODS: Anaesthetics in urine and breathing area were monitored in 124 subjects in 11 operating theatres. Passive samplers were collected after 2.5-7 h of exposure, at the same time as post-shift urinary samples, to evaluate the individual time-weighted average (TWA) exposures to sevoflurane and N(2)O. A static headspace sampler coupled with a gas chromatograph mass spectrometer was used for analytical determinations (sensitivity sufficient to reveal biological/environmental exposures of 0.1 microg/l(urine) and 50 ppb for sevoflurane, and 1 microg/l(urine) and 80 ppb for N(2)O). RESULTS: Median (range) post-shift urinary and environmental values were 1.2 microg/l(urine) (0.1-5.0) and 0.4 ppm (0.05-3.0) for sevoflurane ( n=107) and 10.9 microg/l(urine) (0.5-74.9) and 8.6 ppm (0.2-123.4) for N(2)O ( n=121) (all low-exposure range). At log-log regression, urinary levels closely correlated with environmental data (sevoflurane, r(2)=0.7538; N(2)O, r(2)=0.8749). Biological equivalent limits (BELs) based on National Institute for Occupational Safety and Health (NIOSH) TWA exposure limits, calculated as means of regression slope and y-intercept, were 3.6 microg/l(urine) for sevoflurane (corresponding to 2 ppm) and 22.3 microg/l(urine) for N(2)O (corresponding to 25 ppm). Individual "mixture BELs", which we calculated by applying the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) mix formula to biomarker values and using the obtained NIOSH-based BELs as a reference, closely correlated with mixture TLVs (rho=0.816, Lin's concordance test). CONCLUSIONS. We propose urinary sevoflurane as a new, specific, internal dose biomarker for routine biological monitoring of personal exposures among operating-theatre personnel, and use of reliable "mixture BELs" to provide safer levels of internal exposure for workers exposed to mixtures of sevoflurane and N(2)O, and conceivably also to other mixtures of toxicants with possible additive effects.

Environmental Monitoring↗

Serum gonadotropins and testosterone in men occupationally exposed to carbon disulfide.

Serum levels of gonadotropins and testosterone were determined for 69 men exposed to CS2 in viscose rayon production and for 22 nonexposed male controls. Mean ages of the two groups were 40 and 39 yr, respectively. The duration of exposure to CS2 ranged from 1 to 36 yr (mean, 12.5). Follicle stimulating hormone (FSH) levels were significantly higher among the exposed men than among the controls (13.6 versus 10.0 IU/l). The level of sex hormone binding globulin (SHBG) was significantly lower among the exposed men than among the controls (44 versus 53 nmol/l). Luteinizing hormone (LH) values were significantly higher among the 24-31 yr old exposed men than the controls of the same age. Levels of SHBG, of the free testosterone index, and of FSH and LH in men under 39 yr who had been exposed to CS2 for 1-9 yr differed significantly from those of their controls, whereas only FSH differed significantly among those exposed for 10 or more years in the same age group. In men aged 40 yr or more, after at least 10 yr of exposure, only FSH and LH were significantly higher than in the controls. Although the observed alterations do not seem to have any overt clinical implications for the study groups, they indicate that overall levels of CS2 that are well below the current Finnish threshold limit value (30 mg/m3) may affect the hormonal balance in the pituitary-gonadal axis, favoring the view that there may be an increased risk of latent primary gonadal insufficiency.

Adult↗

Sensory irritation structure-activity study of inhaled aldehydes in B6C3F1 and Swiss-Webster mice.

The sensory irritation potential of a series of saturated and unsaturated aliphatic and cyclic aldehydes was investigated in B6C3F1 and Swiss-Webster mice. With the reflex decrease in respiratory rate as the endpoint response, alpha, beta-unsaturated aliphatic aldehydes yielded RD50 values (concentration which elicits a 50% decrease in respiratory rate) ranging from 1 to 5 ppm while saturated aliphatic aldehydes with two or more carbons produced RD50 values from 750 to 4200 ppm. Cyclic aldehydes produced intermediate RD50 values which ranged from 60 to 400 ppm. No statistically significant differences were found between concentration-response curves of B6C3F1 and Swiss-Webster mice. Saturated aliphatic aldehydes with two or more carbons were nearly 1000 times less potent than formaldehyde. Although the mechanisms responsible for stimulation of trigeminal nerve endings by airborne chemicals are poorly understood, several hypotheses may help to explain the differences seen in this study. For example, the sensory irritation potency of the saturated aliphatic aldehydes diminished with their reported dehydration constants which may determine the degree to which these aldehydes crosslink with receptor proteins. The sensory irritation potency of acrolein and crotonaldehyde was probably due to 1,2 or 1,4 addition reactions. Additionally, molecular conformation and a recently published physical mechanism may contribute to sensory irritation responses, particularly for the less reactive aldehydes. Tentative threshold limit values (TLVs), based upon prevention of sensory irritation, were extrapolated from the RD50 values of Swiss-Webster mice. With the exception of crotonaldehyde, good agreement was found with currently published TLVs.

Aldehydes↗

Neurophysiological changes in workers exposed to organic solvents in a shoe factory.

Motor conduction velocity (MCV) was measured in the median, ulnar, and peroneal nerves of 52 referents and 95 workers from a shoe factory, in a search for dose-effect and dose-response relationships between exposure to organic solvents and subclinical impairment of the peripheral nervous system (PNS). According to the environmental concentrations, the exposure was expressed as the sum of the products between the median hygienic effect (ranging from 0.08 to 2.89) and worktime (from 1 to 29 a) in every job. The motor action potential (MAP) amplitudes, durations and shapes of the exposed workers were significantly affected even if to a different extent and significance level when compared to those of the MCVs of the referents. The MCVs of the median (t = 3.17, p less than 0.01) and peroneal (t = 2.11, p less than 0.05) nerves were reduced as compared to reference values. In the exposed group, the MCV of the median nerve was negatively correlated with exposure score (r = 0.45, p less than 0.01) but not with age. No relationship was found between MVCs of the ulnar and peroneal nerves and exposure. The MCV of the median nerve was particularly slow in a subgroup of workers with an exposure score of greater than 20 (t = 2.30, p less than 0.05 vs the other exposed workers; t = 5.56, p less than 0.01 vs the referents). This exposure score represents only 50% of the maximum allowable score for a worktime of 40 a. Even if none of the examined workers showed clinical signs of polyneuropathy, evidence of subclinical effects on the PNS were found among subjects with long-term exposure to hexacarbon mixtures. Therefore, our results suggest the need for a lowering of current threshold limit values at least for n-hexane.

Adolescent↗

Urine, serum and hair monitoring of hydrofluoric acid workers.

To define the relationship between fluoride (F) concentration in the serum, urine and hair of workers and the concentration of hydrofluoric acid (HF) in the work environment, pre- and postshift serum and urine samples of 142 HF exposed workers and 237 unexposed workers were examined. Hair specimens were also collected for the determination of F. To determine whether external contamination influences hair analysis, the control hair samples were kept in the work environment for one week. The pre-exposure levels in serum and urinary F in HF workers were higher (P < 0.01) than the control values. This suggests that F excretion from the body continues for at least 12 hours. The postshift serum and urinary F concentrations of these workers were significantly higher (P < 0.01) than the preshift concentrations. The levels of F in the hair of HF workers were also higher than in the control subjects. The concentrations of F in postshift serum and urine, and hair were in good correlation to each other. There was a linear relationship between mean serum and urinary F concentrations and HF concentration in the workplace. A mean F concentration of 82.3 micrograms/l in serum and 4 mg/l in urine with a lower fiducial limit (95%, P = 0.05) of 57.9 micrograms/l in serum and 2 mg in urine were estimated to correspond to an atmospheric HF concentration of 3 ppm, which is the maximum allowable concentration recommended by Japan Association of Industrial Health and also the threshold limit value suggested by American Conference of Governmental Industrial Hygienists.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗