Progress toward the elimination of hepatitis B virus transmission among health care workers in the United States

BACKGROUND: Hepatitis B virus (HBV) infection is a well-recognized occupational risk for health care workers (HCWs). Vaccination coverage, disease trends, and the need for booster doses after hepatitis B vaccination of adults have been the subject of intense study during the 15 years of the vaccine's availability. METHODS: Vaccination coverage of HCWs was determined from a review of medical records on a sample of employees from 113 randomly selected hospitals. The number of HBV infections among HCWs and the general US population for 1983 through 1995 was estimated from national surveillance data. Studies on long-term protection after hepatitis B vaccination of adults were reviewed. RESULTS: A total of 2837 employee medical records were reviewed; 2532 employees (90%) were eligible to receive hepatitis B vaccine, and 66.5% of them (95% confidence interval, 61.9%-70.9%) had received 3 doses of hepatitis B vaccine. Vaccination coverage was highest (75%) for personnel with frequent exposure to infectious body fluids (phlebotomists, laboratory personnel, and nursing staff) and lowest (45%) for employees at low risk for exposure (dietary and clerical staff). The number of HBV infections among HCWs declined from 17,000 in 1983 to 400 in 1995. The 95% decline in incidence observed among HCWs is 1.5-fold greater than the reduction in incidence in the general US population. Studies on long-term protection demonstrate that vaccine-induced protection persists at least 11 years even when titers of antibody to hepatitis B surface antigen decline below detectable levels. CONCLUSIONS: Although a high percentage of HCWs have been fully vaccinated with hepatitis B vaccine, efforts need to be made to improve this coverage. There has been a dramatic decrease in the number of HBV infections among HCWs who are now at lower risk of HBV infection than the general US population. Vaccine-induced protection persists at least 11 years and booster doses are not needed at this time for adults who have responded to vaccination.     

A model for interval-censored tuberculosis outbreak data

As the incidence of tuberculosis (TB) has increased in the United States, occupationally acquired TB has increased among the health care workers (HCWs). This paper describes a model developed in response to the needs of an outbreak of multidrug-resistant TB. One of the goals of the outbreak investigation was to estimate the risk of tuberculin skin test (TST) conversion as a function of HCW job type and the period during which persons were employed over the study period. TST conversions were evaluated at periodic examinations and data are interval-censored. We present a generalized linear model that extends Efron's survival model for censored survival data to the case of interval-censored data.     

Postexposure prophylaxis after nonoccupational HIV exposure: clinical, ethical, and policy considerations

In the wake of recent breakthroughs in antiviral therapies and Centers for Disease Control and Prevention (CDC) recommendations advocating occupational postexposure prophylaxis (PEP), health care workers are increasingly receiving inquiries about PEP following exposures to the human immunodeficiency virus (HIV) through sex and injection drug use. The probability of HIV transmission by certain sexual or injection drug exposures is of the same order of magnitude as percutaneous occupational exposures for which the CDC recommends PEP. In such cases, if the exposure is sporadic, it seems appropriate to extrapolate from the data on occupational PEP and recommend prophylaxis. However, for individuals with continuing or low-risk exposures, we instead recommend referrals to state-of-the-art risk reduction programs. Clinicians, using local HIV seroprevalence data and their knowledge of transmission probabilities, can help exposed patients make an informed decision regarding PEP. Because of the large number of risky encounters that will not be treated prophylactically, even after significant outreach efforts, public health interventions that emphasize PEP as part of a comprehensive HIV prevention program should be confined to cities with highest HIV prevalences.     

Estimation of reference values for urinary 1-hydroxypyrene and alpha-naphthol in Danish workers

In order to assess environmentally and occupationally related exposures to PAH compounds it is essential to have reference or normal values in human body fluids. The establishment of reliable reference intervals is an absolute pre-requisite in determining relationships between internal PAH exposure in humans and health effects in occupationally exposed workers. In this context the estimation of the biological level of PAH metabolites in urine from reference populations has become increasingly important in the field of environmental and occupational toxicology. The present study describes the calculation of tentative reference values for urinary 1-hydroxypyrene on the basis of two reference populations and for urinary alpha-naphthol on the basis of one reference population in accordance with IFCC recommendations. The study subjects were 115 healthy male workers occupationally exposed to PAH at low levels and 121 reference subjects non-occupationally exposed to PAH. Tentative reference values for urinary 1-hydroxypyrene were estimated. In addition, 236 healthy male workers were used to estimate tentative reference values for urinary alpha-naphthol. The reference populations were described by distribution free one-sided tolerance intervals. The 95% one-sided tolerance limit calculated for 1-hydroxypyrene in urine was 0.053 mumol/mol creatinine for non-occupationally exposed individuals and 0.169 mumol/mol creatinine for low level PAH exposed workers, with the coverage interval (95 +/- 4.5) percent at a probability of 0.95. Thus, the probability was 0.975 that the tolerance interval included at least 90.5% of the distribution. In addition, the probability was 0.025 that the tolerance interval included > 99.5% of the population. The tolerance interval for alpha-naphthol in urine was 5.665 mumol/mol creatinine with the coverage interval (95 +/- 4.5) percent at a probability of 0.95.     

Mandibular fractures following third molar extraction. A retrospective clinical and radiological study

Health care workers (HCW) are at risk of occupationally acquiring Mycobacterium tuberculosis (TB) infection. The Centers for Disease Control and Prevention has published guidelines for health care facilities to protect HCW. One of the recommended elements is TB infection surveillance among HCW using purified protein derivative (PPD) skin testing and analysis of the data by occupational group and work location to determine areas of increased risk of infection. At the military medical center (MMC) we studied, occupational groups with statistically significant (p < 0.05) above-average PPD conversion risk (> 1.1%/year) included respiratory therapists (15.6%/year), nursing technicians (2.3%/year), and military personnel (1.6%/year). Maintenance and engineering workers (2.6%/year), food service workers (2.5%/year), laboratory workers (2.0%/year), custodial workers (1.8%/year), and practical nurses (1.7%/year) had above-average, but not statistically significant, risk. The fourth floor of the MMC had 39% (21/54) of the converters. The surveillance program also uncovered 235 individuals who had not completed adequate prophylactic therapy, and a case of active TB in a laboratory worker.     

Prediction of response to hepatitis B vaccine in health care workers: whose titers of antibody to hepatitis B surface antigen should be determined after a three-dose series, and what are the implications in terms of cost-effectiveness?

We identified the demographics of 385 health care workers (HCWs) to identify those whose chance of developing a protective response to a standard primary hepatitis B immunization series was so high that the need for testing for antibodies to hepatitis B surface antigen (anti-HBs) would be obviated following immunization. In addition, using sensitivity analysis, we analyzed the economic consequences of not determining anti-HBs titers for any individual after primary immunization and of using the Centers for Disease Control and Prevention (CDC)-recommended post-hepatitis B exposure prophylaxis for high-risk HCWs. Nonsmoking women < 50 years old with a weight-height index of < 42 had a 98.2 +/- 0.9% chance of developing a protective anti-HBs titer. Male nonsmokers < 50 years old with a weight-height index of < 29 had a 94.7 +/- 1.8% chance of a protective response. Economic analysis revealed that use of the CDC guidelines for post-hepatitis B exposure prophylaxis in male HCWs whose anti-HBs status is unknown is always more cost-effective than determining anti-HBs titers following primary immunization for those at high risk. In female HCWs, post-hepatitis B exposure prophylaxis is more cost-effective until hepatitis B exposure rats are approximately 50%. It is possible to predict who will have a high probability of developing a protective response to hepatitis B vaccine; for these people, determining postimmunization anti-HBs titers is unnecessary and not cost-effective.     

Association between centromeric deletions of the SMN gene and sporadic adult-onset lower motor neuron disease

OBJECTIVE: To identify risk factors for polymicrobial bloodstream infections (BSIs) in neonatal intensive care unit (NICU) patients during an outbreak of BSIs. DESIGN: During an outbreak of BSIs, we conducted a retrospective cohort study, assessed NICU infection control practices and patient exposure to NICU healthcare workers (HCWs), and obtained cultures of the environment and HCW hands. PATIENTS: During the period May 3 to 7, 1996, 5 infants contracted BSIs caused by both Enterobacter cloacae and Pseudomonas aeruginosa, and one infant contracted a BSI caused by E cloacae only. For each pathogen, all isolates were identical on DNA typing. RESULTS: Infants exposed to the following were more likely than nonexposed infants to have BSI: umbilical venous catheters (6/14 vs 0/7, P = .05), total parenteral nutrition given simultaneously with a dextrose/electrolyte solution (6/12 vs 0/9, P = .02), or one HCW (5/7 vs 1/13, P = .007). Neither environmental nor HCW hand cultures yielded the outbreak pathogens. Quality control cultures of intravenous solution bags were negative. CONCLUSIONS: We speculate that a dextrose multidose vial became contaminated during manipulation or needle puncture and that successive use of this contaminated vial for multiple patients may have been responsible for BSIs. Aseptic techniques must be employed when multidose vial medications are used. Single-dose vials should be used for parenteral additives whenever possible to reduce the risk of extrinsic contamination and subsequent transmission of nosocomial pathogens.     

Occupational exposure to organic solvents and sleep-disordered breathing

STUDY OBJECTIVE: To investigate whether people with occupational exposure to organic solvents have a higher prevalence of obstructive sleep apnea syndrome (OSAS) than the general population and to examine the relationship between snoring and exposure to organic solvents. DESIGN AND PARTICIPANTS: Consecutive patients, aged 30-64 years, referred during a 3-year period to the sleep laboratory at Avesta Hospital, Sweden, because of suspected OSAS made up the patient groups. Following admission, patients underwent a simplified sleep apnea investigation and were divided into two groups, OSAS (n = 320) and snorers (n = 443). A random sample of 296 men and 289 women aged 30-64 years obtained from a register of all country residents maintained by the county tax authority served as referents (controls). Both patients and referents responded to two questionnaires, including questions about occupation, exposure to organic solvents, and other chemical and physical agents. RESULTS: Men with OSAS or snoring and women with snoring had more often been occupationally exposed to organic solvents than the referents, showing an almost twofold increase in risk for those exposed during whole workdays. For men, the risk of OSAS or snoring increased with increasing exposure. CONCLUSION: The result indicates that occupational exposure to organic solvents might cause sleep apnea. A new observation is that even snoring could be caused by exposure to organic solvents. It is important to elucidate whether exposure to organic solvents is a cause of OSAS, because such a finding may have important implications for prevention and treatment of sleep disturbances.     

Renal cell cancer correlated with occupational exposure to trichloroethene

A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer with special emphasis on C2HCl3 and the structurally and toxicologically closely related compound tetrachloroethene (C2Cl4). A group of 84 patients from the accident wards of three general hospitals in the same area served as controls. Of the 58 cases, 19 had histories of occupational C2HCl3 exposure for at least 2 years and none had been exposed to C2Cl4; of the 84 controls, 5 had been occupationally exposed to C2HCl3 and 2 to C2Cl4. After adjustment for other risk factors, such as age, obesity, high blood pressure, smoking and chronic intake of diuretics, the study demonstrates an association of renal cell cancer with long-term exposure to C2HCl3 (odds ratio 10.80; 95% CI: 3.36-34.75).     

Human blood samples as indicators of occupational exposure to persistent chlorinated hydrocarbons

The value of using human blood as an indicator of occupational exposure to persistent organochlorine compounds is demonstrated. Blood samples from a total of 35 persons divided into three different groups, with and without exposure to chlorinated hydrocarbons in the work atmosphere, have been investigated by gas chromatography using electron capture detection. It is shown that the group of workers with an occupational exposure to pentachlorobenzene, hexachlorobenzene, heptachlorostyrene and octachlorostyrene had a higher level of these chlorinated hydrocarbons in their blood samples than did the other groups. On the average, the concentration of hexachlorobenzene is about 20 times higher in blood samples from the occupationally exposed workers than from the control group. The level of hexachlorobenzene in blood samples of the control groups is low compared to recent studies of blood samples from the general population in other industrialized countries. Furthermore, the average value obtained for the exposed workers is of the same magnitude as the general population in these industrialized countries.     

Detection of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, in white blood cells of workers occupationally exposed to styrene

Styrene-7,8-oxide (SO), the major in vivo metabolite of styrene, is a genotoxic compound and a potential carcinogenic hazard to occupationally exposed workers. The aim of the present work was to investigate the ability of styrene exposure to induce formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in white blood cells (WBC) of boatbuilders occupationally exposed to styrene. The study of these adducts was conducted to see if styrene exposure can cause oxidative damage of DNA. The 8-OHdG/10(5) dG ratio from 17 styrene-exposed workers showed significant increases (mean +/- SD, 2.23 +/- 0.54, median 2.35, P < 0.001) in comparison to the controls (1.52 +/- 0.45, median 1.50). However, 11 out of 17 workers who were between the ages of 32 and 60 years and had been occupationally exposed to styrene for > 10 years showed higher 8-OHdG/10(5) dG ratios (2.31 +/- 0.62, median 2.37) in comparison to 6 workers with < 6 years of occupational styrene-exposure (2.11 +/- 0.36, median 2.05; P > 0.05, no significant difference between the two groups of workers). The studies presented here provide an indication that styrene exposure can result in oxidative DNA damage.     

Design, construction, implementation, and cost of a hospital pharmacy cleanroom

The authors sought to clarify in a cross-sectional study the possible associations between homeostatic regulators of calcium and occupational exposure to lead. Subjects were 146 industrial male employees, 56 with and 90 without occupational lead exposure. The main outcome measures were serum concentration of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitriol). The median values of blood lead were 40.5 microg/dl in the exposed group and 4.0 microg/dl in the controls. There were no differences between groups in dietary history and serum calcium levels. PTH and calcitriol levels were significantly higher in the exposed than in the nonexposed subjects (42.0+/-24.2 vs. 33.6+/-14.9 pg/ml, p <0.05; and 83.8+/-27.0 vs. 67.9+/-17.6 pmol/liter, p <0.001, respectively). Multivariate analyses showed that after controlling for possible confounders, occupational lead exposure (no/yes) was independently associated with PTH level (pg/ml) (beta = 7.81, 95% confidence interval (CI) 3.7-11.5) and with calcitriol (pmol/liter) (beta = 12.3, 95% CI 3.84-20.8). It is concluded that subjects occupationally exposed to lead show a substantial compensatory increase in PTH and calcitriol activities which keep serum calcium levels within normal range. This may be of clinical significance since a sustained increase in calcitropic hormones in susceptible subjects may eventually increase the risk of bone disorders.     

Influence of feed restriction in primiparous lactating sows on body condition and metabolic parameters

Bearing in mind a great diffusion of electromagnetic fields (EMF) with power-line frequency (in Poland-50 Hz) both in the occupational and communal environments, it is not surprising that possible health effects related to this exposure evoke much interest. Electromagnetic fields may affect the circulatory and nervous systems because of theoretical probability that electric impulses, generated by external electric and magnetic fields, may disturb their functions. For this reason we have decided to evaluate the functioning of the circulatory system in persons occupationally exposed to power-line frequency electromagnetic fields by employing the most up-to-date methods facilitating the in-depth diagnosis of the circulatory system and neurovegetative mechanisms. The work presented focused on the evaluation of electrocardiographic changes. The study covered 63 workers of the transforming and distributing stations, aged 22-67 years (median 39 +/- 10), employed under exposure for 2-43 years (median 15 +/- 10). The control group consisted of 42 workers of radio link stations, aged 23-65 years (median 30 +/- 14), employed in the similar system but not exposed to EMF, with employment duration of 1-42 years (median 13 +/- 4). All persons were subject to general medical examinations, resting ECG, and 24 h Holter monitoring. In addition, the level of exposure in individual workplaces was estimated following the measurements of the intensity of electric and magnetic fields. In workers of electromagnetic stations an increased risk for electrocardiographic disturbances was revealed. Under conditions of exposure to electric fields, observed in stations where workers were employed, the risk was increased by 10%.     

Renal failure in two patients with Wolfram syndrome

BACKGROUND/OBJECTIVE: Aluminium is produced from the mineral bauxite. Occupational exposure is reported during the industrial processing of aluminium and is associated with pulmonary and neurotoxicity. However, data on exposure and toxicity of workers in the open bauxite mining industry do not exist. Therefore, a study was performed to explore aluminium exposure in employees involved in this bauxite mining process in a Surinam mine. METHODS/DESIGN: A group of workers occupationally exposed to aluminium in an open bauxite mine were compared with a group of nonexposed wood processors. Serum aluminium was analyzed using atomic absorption spectrometry Data from the clinical chemistry of the blood and a questionnaire were used to explore determinants for aluminium exposure. RESULTS: No significant difference between serum aluminium in the exposed (4.4 +/- 2.0 micrograms/L, n = 27) and control group (5.1 +/- 1.5 micrograms/L, n = 27) was detected. For the serum concentration of the clinical chemical variables (calcium, citrate, and creatinine), a statistically significant difference was computed (p < or = 0.02) between the exposed and control group. All levels were slightly higher in the exposed group; no statistically significant correlations with serum aluminium were found. CONCLUSIONS: In this study, serum aluminium values were in the normal range, no significant difference between the groups could be detected despite long-term occupational exposure.     

In situ expression of ICAM-1 and its mRNA in the lung tissue of asthmatic rats

The objective of this work was to determine whether the prevalence of respiratory symptoms differed among workers exposed to different types of metal-working fluids. As part of a mandatory surveillance system for occupational illness, from 1988-1994, the Michigan Department of Public Health received, 86 occupational disease reports of work-related asthma secondary to exposure to metal-working fluids. As part of a public health program, follow-up industrial hygiene inspections, including medical interviews of the workforce, were performed at companies where the reported cases had become ill. Metal-working fluids were the second most common cause of work-related asthma reported in the state. Most of the reports were from the automobile industry. Follow-up inspections were conducted at 37 facilities where the individuals with work-related asthma had worked. Seven hundred and fifty-five workers at these facilities were interviewed. Only one facility was above the allowable oil mist standard. Despite the exposure levels being within the legal limits, approximately 20% of the fellow workers of the reported cases had daily or weekly respiratory symptoms suggestive of work-related asthma. Workers exposed to emulsified, semisynthetic, or synthetic machining coolants were more likely to have chronic bronchitis; to have visited a doctor for shortness of breath; to have visited a doctor for a sinus problem; to be bothered at work by nasal stuffiness, runny nose, or sore throat; and to have an increased prevalence of respiratory symptoms consistent with work-related asthma, compared to workers exposed to mineral oil metal-working fluids. These findings were found in individuals who currently smoked, had never smoked or were ex-cigarette smokers. Further research to determine the chemical components or microbial contaminants responsible for these findings is needed.     

Clinical, laboratory, phototest and phototherapy findings in polymorphic light eruptions: a retrospective study of 133 patients

OBJECTIVE: To study the blood benzene levels resulting from environmental and occupational benzene exposure. METHODS: Benzene in venous blood was measured in 243 nonoccupationally exposed subjects ("normal" people) and in 167 workers occupationally exposed to benzene. All exposed workers gave blood samples at the end of the work shift and on the following morning before resuming work. Blood benzene was assayed by gas chromatography (GC)-mass spectrometry. Occupational benzene exposure was monitored by environmental personal samplers and measured by GC analysis. RESULTS: The mean occupational benzene exposure for all 167 workers studied was 186 ng/l (58 ppb; range 5 1535 ng/l, 2-500 ppb). Overall, the mean blood benzene level of all workers was 420 ng/1 at the end of the shift and 287 ng/l on the morning thereafter. The blood benzene levels measured the morning after turned out to be significantly lower (t=3.6; P < 0.0001) than those measured at the end of the shift. The mean blood benzene level of the 243 "normal" subjects was 165 ng/l, which was significantly lower than that measured in the workers on the morning thereafter (t=5.8: P < 0.0000001). The mean blood benzene concentration was significantly higher in smokers than in nonsmokers in both the general population (264 versus 123 ng/l) and in the exposed workers. In the group of nonsmoking workers, whose workplace exposure to benzene was lower than 100 ng/l, blood benzene levels were similar (210-202 ng/l) to those measured in the nonsmoking general population (165 ng/l). End-of-shift blood benzene correlated significantly with environmental exposure (y=0.91x + 251; r=0.581; n=162; P < 0.00001). Finally, there was also a significant correlation between blood benzene measured at the end of the shift and that determined on the morning thereafter (y=0.45x + 109; r=0.572; n=156; P < 0.00001). Conclusion: Nonsmoking workers occupationally exposed to benzene at environmental levels lower than 100 ng/l (mean 35 ng/l) and the nonsmoking general population exposed to ubiquitous benzene pollution have similar blood benzene concentrations. This suggests that it is impossible to distinguish between occupational and environmental exposure when the benzene level in the workplace is less than 100 ng/l.     

The merits of varicella vaccination for varicella non-immune health care workers

Immunity against varicella can be reliably established by history and, if negative, confirmed or refuted by serology. If non-immune, the merits of varicella vaccine for a health care worker (HCW) can be stated clearly: Protection from a disease which may be particularly severe in an adult, and evading the inconvenience (investigation time and possible work restriction) and cost of managing an exposure. This paper discusses implementation of a varicella immunity program for HCWs at Columbia Presbyterian Hospital in Oklahoma City.     

The risk of exposure to potentially contaminated body fluids in urological surgery

To determine the risk of exposure to body fluids potentially contaminated with infectious organisms we instituted a prospective study of all urological procedures performed at our institution. Urological procedures were divided into 3 categories: open, cystoscopic and endoscopic surgical (transurethral resection of the prostate or bladder tumor, ureteroscopy and percutaneous procedures). We have complete data analysis on 594 consecutive patients who underwent an operation at our institution: 77 (13%) underwent an open procedure, 75 (13%) underwent an endoscopic surgical procedure and the remaining 442 (74%) underwent cystoscopic procedures. All procedures were performed by supervised house staff using universal precautions. The operating surgeon was exposed to potentially contaminated body fluids in 173 of 594 cases overall (29%). There was exposure in 17% of all open procedures, 41% of all endoscopic surgical procedures and 29% of all cystoscopic procedures. Urologists must consider themselves at high risk for exposure to potentially contaminated body fluids and take appropriate precautions.     

Sleepiness as measured by modified multiple sleep latency testing varies as a function of preceding activity

Although female breast cancer rates are lower in China than in Western countries, rates have been rising rapidly in China. This increase may be due to changes in established breast cancer risk factors, but it is possible that exposure to occupational and environmental carcinogens in Shanghai also have contributed to the rise in incidence. We used data collected by the Shanghai Cancer Registry and the Chinese Third National Census to study the risk of breast cancer by occupation and by occupational exposures. Standardized incidence ratios (SIRs) were used to compare observed cases to expected numbers of cases, based on the incidence rates for Shanghai and the number of women in each occupation according to the 1982 census. Statistically elevated SIRs for breast cancer were seen for a number of professional occupational categories, with the greatest risk seen among scientific research workers (SIR = 3.3). Administrative clerks, political and security personnel, and makers of rubber and plastics products also had significant excesses. Significant deficits of risk were seen for the categories of production and related workers, construction workers, and transportation equipment operators. For specific occupations, the highest SIRs were observed among doctors of Chinese-Western medicine (SIR = 14.7, 95% CI = 5.9-30.3) and doctors of Chinese medicine (SIR = 7.2, 95% CI = 4.4-11.4). We also found excesses among teachers at each level of education, librarians, clerical workers, electrical and electronic engineers, nurses, lab technicians, accountants and bookkeepers, rubber manufacturing products makers, weavers, and knitters. SIRs were significantly elevated for high probability of exposure to organic solvents (SIR = 1.4). For benzene exposure, we found significant excesses for overall exposure (SIR = 1.1) and for medium level of exposure (SIR = 1.3). There was no evidence of an association between risk and electromagnetic fields (EMF) exposure. Based on a small number of exposed, SIRs were elevated for both medium probability and high level of exposure to pesticides. The elevations in occupations reported here support some previous reports. Our finding of an increased risk associated with benzene also has been reported previously; the finding for organic solvents is new. However, the literature on the risk of breast cancer related to occupational exposures is limited and there is no consistent body of literature for any of the exposures studied here. Further, many comparisons were made and the problem of multiple hypothesis testing cannot be ignored in a survey such as ours.     

Ethylene glycol ethers and risks of spontaneous abortion and subfertility

Potential reproductive effects from occupational exposures to ethylene glycol ethers (EGE) are of concern since these organic solvents have been used widely in industry, and their reproductive toxicity has been well documented in animal studies. For determination of whether occupational exposure to EGE was associated with increased risks of spontaneous abortion and subfertility (i.e., taking more than 1 year of unprotected intercourse to conceive), a retrospective cohort study was conducted among workers at two semiconductor manufacturing plants in the eastern United States in 1980-1989 as part of a larger evaluation of reproductive health. Reproductive and occupational histories were obtained from interviews of semiconductor manufacturing workers and spouses. Assessment of potential exposure to mixtures containing EGE (none, low, medium, and high) was based on reported processes and company records. There were 1,150 pregnancies to semiconductor manufacturers, 561 to female employees and 589 to wives of male employees. Among female manufacturers, potential exposure to mixtures containing EGE was associated with increased risks of spontaneous abortion (relative risk in the high exposure group = 2.8; 95% confidence interval (CI) 1.4-5.6) and subfertility (odds ratio in the high exposure group = 4.6; 95% CI 1.6-13.3). Both of these risks exhibited a dose-response relation with potential EGE exposure (p for trend = 0.02). Among spouses of male manufacturers potentially exposed to mixtures containing EGE, there was no increased risk of spontaneous abortion, but there was a nonsignificant increased risk of subfertility (odds ratio in the high exposure group = 1.7; 95% CI 0.7-4.3).