Current Threshold Limit Value Research Articles

Histopathological study in B6C3F1 mice chronically exposed by inhalation to glutaraldehyde

Glutaraldehyde vapors are irritating for the skin, eyes, nose and lungs; respiratory symptoms and headaches have been described among workers exposed to low concentrations of glutaraldehyde far below to 190 ppb. This study was initiated to determine the chronic effects in mice of inhaled glutaraldehyde vapors. B6C3F1 mice were exposed using whole-body inhalation chambers, 6 h/day, 5 days/week, for 52 and 78 weeks to 100 ppb, or to filtered air (controls). In nasal passages at the level of the vestibule, hyperplasia of the squamous epithelium lining of the dorsal wall and lateral aspect of the atrioturbinate was observed in a greater number of exposed females than in controls. Epidermal erosion and ulceration as well as squamous and inflammatory exfoliation were also seen in the nasal lumens. All these changes were dependent on the length of glutaraldehyde exposure. The present data suggest that glutaraldehyde long term exposure only led to changes in nasal passages of female mice but did not induce mortality and/or tumors in nasal passages, in all mice. These results, along with the previous subchronic inhalation study of Gross et al., 1994, demonstrates that in a long term study, chronic glutaraldehyde exposure close to the current threshold limit values induced lesions at the more anterior part of the nasal passages in mice and that they likely result from an irritation mechanism (antero-posterior gradient).

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.

97/04202 Municipal sludge use in coal mine reclamation and potential effects on the formation of acidic mine drainage

Olfactory Mucosal Lesions in F344 Rats Following Inhalation Exposure to Pyridine at Threshold Limit Value Concentrations. Nikula, K. J., and Lewis, J. L. (1994). Fundam. Appl. Toxicol. 23, 510-517.Pyridine is a volatile solvent used as an intermediate in the production of insecticides, herbicides, pharmaceuticals, and dyes. Pyridine is also found in tobacco smoke. Because inhalation is a primary route of exposure to pyridine, we examined the effect of inhaled pyridine on morphology at the portal of entry, the nose. Nasal tissues from F344/N rats exposed using a nose-only mode 6 hr/day for 4 days to either filtered air (controls) or one of two concentrations of pyridine vapor were examined histologically. The rats had been killed 18 hr after the last exposure. The two pyridine concentrations were the current threshold limit value (TLV, 5 ppm) and a high concentration (444 ppm). Olfactory epithelial lesions in rats exposed to both concentrations of pyridine included vacuolar degeneration of sustentacular cells; focal, marked attenuation of the epithelium; loss of vacuolar degeneration of sustentacullar cells; focal, marked attenuation of the epithelium; loss of neurons; and the presence of intraepithelial luminal structures. The lesions were only slightly more severe in the rats exposed to 444 ppm compared to those rats exposed to 5 ppm pyridine. The results show that inhalation of pyridine at the current TLV concentration of 5 or 444 ppm causes lesions in the olfactory epithelium of rats.

Urinary excretion of specific mercapturic acids in workers exposed to styrene.

Styrene is an important chemical of wide industrial use, particularly in the manufacture of polymers and reinforced plastics. Environmental and occupational exposures to styrene occur predominantly via inhalation. Styrene undergoes biotransformation mainly by side chain oxidation catalyzed by cytochrome P-450 enzymes to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers of styrene oxide can be conjugated with glutathione to both (R)- and (S)-diastereoisomers of specific mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). We conducted this biomonitoring study with the aim of evaluating the association between excretion of specific mercapturic acids (M1 and M2) and level of exposure to styrene among occupationally exposed people. The mean time-weighted average (TWA) exposure was about one-half the current threshold limit value, the range of the values varied from 44 to 228 mg/m3. Geometric mean (GM) concentrations of 650, 1,084, and 31.8 micrograms/g creatinine were measured, respectively, for M1-S, M2, and M1-R. The environmental styrene concentration exhibited a significant correlation with total specific mercapturic acid (Mtot = sum of M1-R, M1-S, and M2), making it possible for the first time to calculate the approximate relationship between styrene uptake and excretion of these substances. The M2 mercapturic acid had a better correlation (r = 0.56) with respect to M1-R and M1-S. Significant correlations were found also between the excretion of specific mercapturic acids and biological exposure indices (i.e., mandelic and phenylglyoxylic acids and urinary styrene).

Polycyclic Aromatic Hydrocarbons and Cancer in Man

Various substances and industrial processes, surrogates of exposure to polycyclic aromatic hydrocarbons (PAHs), are currently classified as human carcinogens. This paper reviews recent epidemiological studies reporting direct evidence of the carcinogenic effects of PAHs in occupationally exposed subjects. Risks of lung and bladder cancer were dose dependent when PAHs were measured quantitatively and truly nonexposed groups were chosen for comparison. These new findings suggest that the current threshold limit value of 0.2 mg/m3 of benzene soluble matter (which indicates PAH exposure) is unacceptable because, after 40 years of exposure, it involves a relative risk of 1.2-1.4 for lung cancer and 2.2 for bladder cancer.

An example for stepwise reduction of work site-induced formaldehyde exposure in pathology

Occupational formaldehyde exposure in pathology depends on the efficiency of the ventilation system in use and may reach concentrations considerably above the current threshold limit values. The reduction of formaldehyde exposure by stepwise improvement of the ventilation system at a pathologist's workplace is presented as an example in this paper. Assessment of formaldehyde concentration by personal air sampling at a workplace originally equipped with a hood ventilation system resulted in values of up to 4 ml/m3 in the pathologist's breathing zone. Lowering the ventilation inlet to the working level by connecting the hood to a suction unit via a flexible hose resulted in an effective reduction of formaldehyde exposure to values of about 0.5 ml/m3. This simple and low-cost technical improvement had some uncomfortable side effects, such as current noise and wind chill, which could only be overcome by installing ventilated work tables according to modern technical standards.

Epidemiological study of the systemic ophthalmological effects of carbon disulfide.

A total of 123 male viscose rayon workers who were exposed to carbon disulfide, and an additional 67 workers who were not exposed to any toxic agent in the working environment, underwent a thorough ophthalmological examination. The relationship between exposure and ophthalmological results was analyzed with univariate and multivariate methods. The most striking findings were strong associations between exposure and the 100-HUE color vision score and excess of microaneurysms in the exposed group. The current threshold limit value appeared to protect against these effects.

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.

Neurobehavioral Effects of Low-Level Methanol Vapor Exposure in Healthy Human Volunteers

Methanol-powered vehicles are being introduced in the United States as a solution to air pollution. This study assessed whether acute exposure to methanol vapor at the current industrial threshold limit value of 200 ppm for 4 hr has adverse effects on human neurobehavioral performance. Twenty-six healthy subjects (15 men, 11 women; ages 26-51 years) were exposed to methanol or water vapor for 4 hr while seated in a chamber. The subjects served as their own controls in a randomized, double-blind study design. The variables assessed were serum and urine methanol and formate levels; visual performance (color discrimination and contrast sensitivity); and neurophysiological (auditory evoked potentials) and neurobehavioral performances. Exposure to methanol increased serum concentrations and urinary excretions of methanol, but did not affect formate levels. Overall visual, neurophysiological, and neurobehavioral test outcomes were not significantly affected, unless certain between-subject variables are considered. Slight effects on P-300 amplitude and Symbol Digit testing were noted. We conclude that acute exposure of healthy people to low concentrations of methanol had little effect on these measures of neurobehavioral performance.

Pulmonary toxicity of nickel subsulfide in F344/N rats exposed for 1–22 days

Repeated inhalation of nickel subsulfide (Ni 3S 2) by F344/N rats for 3 months results in chronic active inflammation in the lung and atrophy of the olfactory epithelium. The primary purpose of this study was to determine early responses of the respiratory tract to inhaled Ni 3S 2 in rats and to track the course of development of such lesions in rats exposed for up to 22 days. A secondary purpose was to obtain an improved estimate of the half-time for clearance of Ni from Ni 3S 2-exposed lungs. Groups of F344/N rats were exposed to 0, 0.6 or 2.5 mg Ni 3S 2/m 3, 6 h/day for 1–22 days. Histopathological changes in nose and lung, as well as biochemical and cytological changes in lung, as measured in bronchoalveolar lavage fluid (BALF) and lung tissue, alveolar macrophage (AM) viability and Ni concentration in lung were evaluated. Inflammatory lung lesions in rats exposed to 2.5 mg Ni 3S 2/m 3 peaked in intensity after 4 days of exposure. Minimal degeneration of the olfactory epithelium was noted in the 2.5 mg Ni 3S 2/m 3-exposed rats after day 4 of exposure, with atrophy of the olfactory epithelium occurring in rats killed at 22 days. Lactate dehydrogenase, β-glucuronidase and total protein in BALF were significantly elevated within 7 days of exposure while alkaline phosphatase activity was significantly depressed. AM viability was significantly reduced after 2 days of exposure. Concentrations of Ni in lung increased rapidly during the first 7 days of exposure, but more slowly thereafter. Lung burden data from this and a previous study suggest a clearance half-time for Ni of 3.5–8 days. Results indicate that Ni 3S 2 is relatively soluble in lung and inhalation of concentrations near the current Threshold Limit Value of 1 mg Ni/m 3 can produce detrimental changes in the respiratory tract of rats after only a few days of exposure.

Decline in annual lung function in workers exposed to asbestos with and without pre-existing fibrotic changes on chest radiography.

To examine whether or not workers with pre-existing mild pulmonary fibrosis have accelerated decline in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC), under low level exposure to chrysotile asbestos. All male workers in two asbestos manufacturing factories were followed up annually for six years to compare their declines in FEV1 and FVC. The values of FEV1 and FVC were divided by the square of the person's height to adjust for body size differences (FEV1/Ht2 and FVC/Ht2, respectively). Annual change was calculated for each subject as a slope of the simple linear regression with FEV1/Ht2 or FVC/Ht2 regressed according to age. Analysis was conducted on 242 middle aged workers who had normal routine spirometry values, normal chest radiographs or mild pneumoconiosis up to 1/2 grade, without changes either in smoking habit or severity of pneumoconiosis during the study period, and with acceptable spirograms in three or more surveys. The occupational environment, in terms of chrysotile asbestos, had been well controlled below the threshold limit value of Japan at that time--namely, 2 fibres/micromilligrams. RESULTS-There was no significant effect from the interaction between pre-existing mild pulmonary fibrosis and low level of exposure to chrysotile asbestos on the accelerated annual decline of FEV1/Ht2, or FVC/Ht2. Fibrosis significantly contributed to annual changes in FEV1/Ht2, even after adjustment for mean FEV1 and smoking. The point estimate of the contribution was - 4.9 ml/m2/y. No significant independent contribution of exposure was found in decline of either FEV1/Ht2 or FVC/Ht2. Pre-existing pulmonary fibrosis is an independent risk factor for accelerated annual decline of FEV1, even when mild and stable. Additional decline due to exposure to chrysotile asbestos is less probable if it is well controlled under the current threshold limit value.

Physiologically-based pharmacokinetic modeling of a mixture of toluene and xylene in humans.

A physiologically-based pharmacokinetic (PBPK) model for a mixture of toluene (TOL) and xylene (XYL), developed and validated in the rat, was used to predict the uptake and disposition kinetics of TOL/XYL mixture in humans. This was accomplished by substituting the rat physiological parameters and the blood:air partition coefficient with those of humans, scaling the maximal velocity for hepatic metabolism on the basis of body weight0.75, and keeping all other model parameters species-invariant. The human TOL/XYL mixture PBPK model, developed based on the quantitative biochemical mechanism of interaction elucidated in the rat (i.e., competitive metabolic inhibition), simulated adequately the kinetics of TOL and XYL during combined exposures in humans. The simulations with this PBPK model indicate that an eight hour co-exposure to concentrations that remain within the current threshold limit values of TOL (50 ppm) and XYL (100 ppm) would not result in significant pharmacokinetic interferences, thus implying that data on biological monitoring of worker exposure to these solvents would be unaffected during co-exposures.

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.

Occupational Exposure and Indoor Air Quality Monitoring in a Composting Facility

The objective of this study was to investigate indoor air quality in a completely covered enclosure used for the aerobic composting of organic wastes originating from vegetable, fruit, and garden refuse. Samples of gases and vapors were taken in the ventilation exhaust ducts. Volatile organic compounds (VOCs) were collected on Tenax absorbent; after thermal desorption they were analyzed by gas chromatography/mass spectrometry. Hydrogen sulfide was determined using Dräger test tubes. Microbial samplings were conducted on four sites inside the hall. Microbes were collected using a modified Anderson high-volume sampler, consisting of two impactor stages. Results indicate that the concentrations of VOCs were rather low; only the limonene level was elevated, but it was still well below the current Dutch provisional threshold limit value. Hydrogen sulfide levels found were also far less than the Dutch threshold limit value. Both total bacteria and gram-negative bacterial counts exceeded the provisional Dutch guideline of 10,000 cfu/m3 for indoor air in the work environment. Furthermore, the number of fungi, for the larger part consisting of the genera Aspergillus and Penicillium, which are known to cause respiratory tract disorders, approached the hazardous exposure level.

Olfactory Mucosal Lesions in F344 Rats Following Inhalation Exposure to Pyridine at Threshold Limit Value Concentrations

Olfactory Mucosal Lesions in F344 Rats Following Inhalation Exposure to Pyridine at Threshold Limit Value Concentrations. Nikula, K. J., and Lewis, J. L. (1994). Fundam. Appl. Toxicol. 23, 510-517. Pyridine is a volatile solvent used as an intermediate in the production of insecticides, herbicides, pharmaceuticals, and dyes. Pyridine is also found in tobacco smoke. Because inhalation is a primary route of exposure to pyridine, we examined the effect of inhaled pyridine on morphology at the portal of entry, the nose. Nasal tissues from F344/N rats exposed using a nose-only mode 6 hr/day for 4 days to either filtered air (controls) or one of two concentrations of pyridine vapor were examined histologically. The rats had been killed 18 hr after the last exposure. The two pyridine concentrations were the current threshold limit value (TLV, 5 ppm) and a high concentration (444 ppm). Olfactory epithelial lesions in rats exposed to both concentrations of pyridine included vacuolar degeneration of sustentacular cells; focal, marked attenuation of the epithelium; loss of vacuolar degeneration of sustentacullar cells; focal, marked attenuation of the epithelium; loss of neurons; and the presence of intraepithelial luminal structures. The lesions were only slightly more severe in the rats exposed to 444 ppm compared to those rats exposed to 5 ppm pyridine. The results show that inhalation of pyridine at the current TLV concentration of 5 or 444 ppm causes lesions in the olfactory epithelium of rats.

Induction of type I hypersensitivity in guinea pigs after inhalation of phthalic anhydride

Guinea pigs were exposed through inhalation to phthalic anhydride (PA) dust at 0.5, 1.0, and 5.0 mg/m3, 3 hours/day for 5 consecutive days. Inhalation challenge with aerosolized phthalic anhydride-guinea pig serum albumin (PA-GPSA) conjugate elicited immediate-onset respiratory reactions in animals exposed to all three levels of dust. Inhalation challenge of a subgroup of animals with phthalic anhydride dust did not elicit an immediate response, as measured by changes in respiratory frequency and plethysmograph pressure. Serologic studies showed that these animals had allergic IgG1a antibody to PA-GPSA. There was a dose-dependent increase in specific IgG antibody activity, as measured by ELISA. Animals exposed to and challenged with 5.0 mg/m3 PA dust had significant numbers of hemorrhagic lung foci. Those animals with the greatest number of foci had high IgG antibody activity to PA, as measured by ELISA. This study showed that exposure to levels of PA dust as low as 0.5 mg/m3, below the current threshold limit value of 6.0 mg/m3, can sensitize animals to produce allergic antibody.

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...

The neuroepidemiology of styrene: a critical review of representative literature.

Because exposure to styrene occurs commonly in some industries and styrene is highly lipid soluble, it is reasonable to be concerned about the possibility that styrene is neurotoxic. Styrene, like many other solvents, volatile anesthetics, and drugs, does, at certain concentrations, produce acute changes in consciousness with consequent alterations of feelings, cognition, and psychomotor functioning. Such acute actions do not imply that styrene also would produce reversible or irreversible damage to the nervous system; the evaluation of long-term exposures to styrene also is necessary to draw conclusions about the full range of neural effects that styrene might produce. To that end, several studies of workers exposed to styrene for up to 30 years have been undertaken in factories in many parts of the world. Epidemiologists have suggested that neuropsychological deficits such as slowing of reaction time, loss of color vision, and vestibulooculomotor dysfunction are reliably induced by styrene at levels near or below current exposure standards, which range from 20 to 50 ppm in most of the world. However, the workers so studied always were described as healthy, and the effects noted were considered to be subclinical. A detailed evaluation of much of the neuroepidemiological literature on styrene (38 papers and related literature), however, indicated that the findings were, almost universally, false positive outcomes due to (1) type I statistical error, (2) the action of some factor other than styrene, and (3) misinterpretation of data. Despite the study of workers exposed for many years, no indications of persisting damage to the nervous system were evident from this review. The conclusions of this review of the neuroepidemiology of styrene are consistent with those based on critical reviews of the solvent literature in general, with specific reference to the probable absence of such an entity as the "painter's syndrome" or "chronic toxic encephalopathy". Because the results on styrene neurotoxicity that provide an inclination to lower the current threshold limit values (TLVs) are false positive findings, there is no scientific basis for a reduction in the current TLV.

Correlation between concentrations of n-hexane and toluene in exhaled and environmental air in an occupationally exposed population.

We determined the correlations between the concentrations of n-hexane and toluene in exhaled and environmental air in the shoe manufacturing industry. Data were collected in 1988 and in 1992 from a total of 265 subjects. Environmental air samples were collected with personal diffusive samplers by adsorption on activated charcoal during exposure and from end-expired air (alveolar air) on cartridges of activated charcoal after exposure. Both compounds were desorbed with carbon disulphide and analysed by gas chromatography. Linear regression analyses showed a good correlation between environmental and end-expired air concentrations (r = 0.82 for n-hexane and r = 0.81 for toluene). These correlations allowed us to calculate the concentrations in expired air corresponding to current environmental limit values. The calculated concentrations in end-expired air that correspond to current environmental threshold limit values of 176 mg m-3 for n-hexane and 377 mg m-3 for toluene are 28 mg m-3 (95% confidence limit, 27-29 mg m-3) and 40 mg m-3 (95% confidence limit, 39-41 mg m-3), respectively. Similar correlations were found when the data from the two study periods were analysed separately.

Evaluation of Waste Anesthetic Gases, Monitoring Strategies, and Correlations Between Nitrous Oxide Levels and Health Symptoms

The release of waste anesthetic gases (WAG) in hospital operating rooms (ORs) was evaluated to determine if staff exposure to nitrous oxide exceeded the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) and investigate possible correlations between symptoms and nitrous oxide exposure. The monitoring strategy consisted of nitrous oxide measurements by personal monitoring of the anesthetists and scrub nurses, and area monitoring at the exhaust grills. In addition, room ventilation rates and carbon dioxide concentrations were measured. Self-administered questionnaires were given to both the operating room personnel and staff on control wards. Nitrous oxide levels exceeded the current TLV of 50 ppm in 4 of 12 ORs. Anesthetists typically received the highest nitrous oxide exposure. There was a strong correlation (r2 = 0.90) for nitrous oxide dosimetry results between anesthetists and scrub nurses, and a fair correlation (r2 = 0.35) between area monitoring results and the anesthetists' personal exposures. Carbon dioxide levels commonly exceeded 1000 ppm on control wards. A correlation between reported symptoms and nitrous oxide exposure was not demonstrated. Reported symptoms more closely correlated with carbon dioxide levels. Nitrous oxide dosimetry of the anesthetists appears to be the only accurate strategy for monitoring human exposure to WAG in an operating room.