DNA repair and cyclin D1 polymorphisms and styrene-induced genotoxicity and immunotoxicity.

1-SO-adenine DNA adducts, DNA single-strand breaks (SBs), chromosomal aberrations (CAs), mutant frequency (MF) at the HPRT gene, and immune parameters (hematological and of humoral immunity) were studied in styrene-exposed human subjects and controls. Results were correlated with genetic polymorphisms in DNA repair genes (XPD, exon 23, XPG, exon 15, XPC, exon 15, XRCC1, exon 10, XRCC3, exon 7) and cell cycle gene cyclin D1. Results for biomarkers of genotoxicity after stratification for the different DNA repair genetic polymorphisms showed that the polymorphism in exon 23 of the XPD gene modulates levels of chromosomal and DNA damage, HPRT MF, and moderately affects DNA adduct levels. The highest levels of biomarkers were associated with the wild-type homozygous AA genotype. The exposed individuals with the wild-type GG genotype for XRCC1 gene exhibited the lowest CA frequencies, compared to those with an A allele (P < 0.05). Cyclin D1 polymorphism seems to modulate the number of leukocytes and lymphocytes in the analyzed subjects. The number of eosinophiles was positively associated with XPD variant C allele and negatively with XRCC1 variant A allele (P < 0.05) and XPC variant C allele (P < 0.05). Immunoglobulin IgA was positively associated with an XRCC3 variant T allele (P < 0.01) and negatively with XPC variant C allele (P < 0.05). Both C3- and C4-complement components were lower in individuals with XRCC3 CT (P < 0.05) and TT genotypes (P < 0.01). Adhesion molecules sL-selectin and sICAM-1 were associated with XPC genotype (P < 0.05). Individual susceptibility may be reflected in genotoxic and immunotoxic responses to environmental and occupational exposures to xenobiotics.

Effects of occupational exposure to styrene on expression of adhesion molecule on leukocytes.

Styrene is an indispensable chemical extensively used in plastic and synthetic rubber industries. Styrene is known to produce various types of hepatotoxic, neurotoxic, and genotoxic effects. Styrene may be immunotoxic by both direct and indirect mechanisms. Measurement of adhesion molecules is a new tool for the investigation of immune system modulation. The aim of this study was to evaluate the association of the expression of the adhesion molecules CD11a, CD11b, CD18, CD54, CD49d, and CD62-L in white blood cells and levels of soluble adhesion molecules ICAM-1 and L-selectin in serum with occupational exposure to styrene. Analyses by flow cytometry revealed elevated levels of most of the assessed adhesion molecules on surfaces of lymphocytes, monocytes, and granulocytes. Expression of the adhesion receptor antigens CD11a on lymphocytes, CD11b on monocytes, and CD18 on granulocytes were unaffected. Workers exposed to styrene had decreased concentrations of sICAM-1 and no changes in concentrations of sL-selectin. Styrene exposure appears to increase activation of the immune system and alter leukocyte adherence. This interaction is a critical first step in immune stimulation and leukocyte-endothelial interaction.

Early indicators of the effect of a breast cancer screening program for low-income women.

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) was developed to increase screening among low-income women who are uninsured or underinsured. This study reports early indicators of the effectiveness of this breast screening program in Iowa. Using data from the Census Bureau and the Iowa Behavioral Risk Factor Surveillance System, we found that racial and ethnic minorities aged 50 to 64 more likely were screened by the NBCCEDP than were their counterparts. Data collected by the Iowa BCCEDP showed a breast cancer detection rate (7.1 per 1,000 women screened) that was at least three times higher than its historical comparison, an indication of the lead time of the screened over the nonscreened population. Predictive values positive (referral and biopsy) and stage distribution were typically higher than for the national program but lower than in other countries. In conclusion, a breast cancer screening program among low-income women can be implemented successfully, judged by early indicators of program effectiveness.

Factors associated with adequacy of diagnostic workup after abnormal breast cancer screening results.

BACKGROUND: Women with certain characteristics, such as those residing in rural areas, are less likely screened for breast cancer. To enhance detection of early breast cancer, it is imperative that all women who have abnormal screening results receive appropriate diagnostic procedures. This study reports differences in receipt of diagnostic services following abnormal screening results. METHODS: Screening and diagnostic data were collected as part of a breast and cervical cancer early detection program aimed at reaching women of lower socioeconomic status. Women with completed diagnostic information after having abnormal screening results were included. We based adequacy of diagnostic services on guidelines from the Society for Surgical Oncology, The Commission on Cancer of the American College of Surgeons, and the Centers for Disease Control and Prevention. Several factors were assessed for their association with adequacy of diagnostic follow-up: income, age, race, education, health insurance status, rural-urban residence, reported breast lump, family history of breast cancer, and clinical beast examination or mammogram results. RESULTS: Overall, 14.1% of the 351 abnormal findings were considered inadequately followed up based on the algorithm used. Eighty percent involved an abnormal finding on a clinical breast examination regardless of the mammogram results. Rural women, those with abnormal clinical breast examination findings but normal or equivocal findings on mammograms, and those who self-discovered a mass were less likely to receive adequate follow-up than were their counterparts in multivariate analysis. Rural women were less likely to receive a biopsy or fine-needle aspiration, although it was indicated. One facility accounted for most of the inadequate follow-up screenings among urban women. CONCLUSIONS: Women who have specific demographic and clinical characteristics were less likely to have received adequate diagnostic services. Breast cancers could have been missed initially as a result of inappropriate follow-up. Further investigation of the clinical scenarios using chart reviews is warranted.

Biomonitoring of occupational exposure to styrene in a plastics lamination plant.

A comprehensive approach to biological monitoring of 44 workers occupationally exposed to styrene in a hand lamination plant was performed by using several end-points: styrene in workplace air, styrene in exhaled air, styrene in blood, DNA strand breaks (SBs) and oxidised bases in mononuclear leukocytes, chromosomal aberrations in lymphocytes, immune parameters and genotyping of polymorphic genes of some xenobiotic-metabolizing enzymes (CYP 1A1, EPHX, GSTM1 and GSTP1). We found a significantly higher number of DNA SBs, measured by a modified comet assay, in mononuclear leukocytes of the styrene-exposed workers compared with results from 19 unexposed controls (P<0.001). A fairly strong correlation was observed between SBs and years of exposure (P<0.001, r=0.545). The styrene-exposed workers also showed a significantly increased frequency of chromosomal aberrations (P<0.0001 for highly exposed group, P<0.004 for medium-exposed group, and P=0.0001 for low-exposed group). The proliferative response of T-lymphocytes stimulated with concanavalin A was significantly suppressed in people exposed to styrene (P<0.05). We recorded a significant increase of the percentage of monocytes in differential white blood cell counts in the exposed group (P<0.05). Using flow cytometry, we found an increased expression of adhesion molecules CD62L, CD18, CD11a, CD11b, CD49d and CD54 in the exposed workers as compared with the control group (P<0.05).

Breast and cervical carcinoma: the correlation of activity limitations and rurality with screening, disease incidence, and mortality.

BACKGROUND: Although screening for breast and cervical carcinoma has been widely accepted as beneficial, specific segments of the population are not receiving these services as frequently as recommended. The objective of this study was to describe differences in breast and cervical screening prevalence among those with activity limitations and those residing in rural areas. Disparities in the incidence rates of in situ breast carcinoma and cervical carcinoma, as well as mortality among rural and urban women, are also described. METHODS: Data from the Iowa Behavioral Risk Factor Surveillance System (BRFSS) and Iowa's Surveillance, Epidemiology, and End Results (SEER) were used to determine the prevalence of screening and adverse outcomes among rural populations. To describe the rural nature of counties, the authors used the number of residents per square mile for each county and classified the results into five groups. Mulitple logistic regression was used to determine the prevalence of screening among those with activity limitations and rural residents. RESULTS: Using the BRFSS, those with activity limitations and those residing in rural Iowa were less likely screened for breast or cervical carcinoma. This translated into a lower in situ breast carcinoma incidence rate and a higher invasive cervical carcinoma incidence rate among rural women relative to their urban counterparts. No differences were found for mortality from these cancers. CONCLUSIONS: Lower screening prevalence among rural residents translated into adverse health outcomes. Interventions for increasing the frequency of screening are described.

Prospective epidemiologic evaluation of laboratory animal allergy among university employees.

OBJECTIVES: Evaluation of incidence and risk factors for development of laboratory animal allergy (LAA) among new hires previously unexposed to lab animals. METHODS: Baseline, 6-month and yearly follow-up, questionnaires, pulmonary functions, and methacholine challenges were collected from 98 never-before occupationally exposed and 90 control laboratory researchers. The two groups were followed between 6 and 36 months. RESULTS: At baseline, there were no differences in atopy, pulmonary functions, or methacholine reactivity between the two groups. The incidence of work-related asthma was comparable in the two groups, approximately 2.5% at 6 months and 4.5% at 24 months. The rate of decline in FEV1 was statistically significantly greater in the animal-exposed than nonanimal-exposed workers, and animal-exposed smokers' FEV1 declined significantly more rapidly than any other groups'. CONCLUSION: Despite the low incidence of laboratory-animal allergy and work-related asthma in this group, this study corroborates previously described interaction between smoking and animal exposure.

Association between female infertility and agricultural work history.

Lifetime industrial and occupational histories of women with a medically-confirmed diagnosis of infertility (n = 281) were compared to a group of postpartum women (n = 216) for risks of infertility. Controlling for age of first pregnancy or self-report of infertility, date of outcome, cigarette use, and employment in other types of industries, women were at increased risk of infertility if they had worked in industries associated with agriculture (OR = 7.0, 95% CI 2.3-20.8; cases = 11.7%, controls = 1.9%). Among the occupations in which women worked prior to outcome, only those in agriculture were at significantly elevated risk (adj. OR = 11.3, CI 2.6-48.8; cases = 10.0%, controls = 0.9%). Among those who resided on a farm, the risk of infertility was significantly increased (adj. OR = 1.8, CI 1.2-2.7; cases = 37.4%, controls = 25.8%) although yearly duration of farm residence was not (adj. OR = 0.99, CI 0.95-1.03). Farm residence did not alter the OR seen in agricultural industries or occupations. The risk of being diagnosed with an ovulatory or tubal factor increased 4-16-fold among those who had worked in agricultural industries or occupations. These data suggest that, as has been established in men, agriculturally-related exposures may be a significant risk for infertility in women.

Occupational exposure of water-plant operators to high concentrations of radon-222 gas.

Water-plant operators may be exposed to high airborne radon-222 (222Rn) concentrations created when 222Rn gas transfers from water to air during the water treatment processes. To evaluate this hazard, we placed yearlong alpha-track radon detectors in 31 water plants. The geometric mean of the annual average airborne 222Rn concentrations was 3.4 pCi L-1 (126 Bq m-3), with a maximum of 133 pCi L-1 (4921 Bq m-3). We assessed the short-term temporal variability of 222Rn by monitoring four water plants continuously for a 3- to 6-day period. Cumulative working level months were estimated for the time workers were in the water plants. Because airborne 222Rn concentrations in water plants can reach levels considered unsafe for underground miners, it would be prudent to monitor airborne 222Rn concentrations in water plants which aerate water as part of their treatment process.

Proportionate mortality study of golf course superintendents.

A proportionate mortality study of a cohort of golf course superintendents was conducted using death certificates for 686 deceased members of the Golf Course Superintendents Association of America who died from 1970 to 1992. White males were included in the study population from all 50 states. The study objective was to compare mortality from this cohort to the general U.S. white male population. The proportionate mortality ratio (PMR) for all types of cancer was 136 (CI: 121, 152). Significant excess mortality from smoking-related diseases was observed. The PMR for arteriosclerotic heart disease was 140, which was significantly elevated (CI: 127, 155). In addition, the PMR for all respiratory diseases was 176 (CI: 135,230), while the PMR for emphysema was 186 (CI: 101,342). The PMR for lung cancer was 117 (CI: 93, 148). Mortality for four cancer types--brain, lymphoma (non-Hodgkin's lymphoma, NHL), prostate, and large intestine--occurred at elevated levels within this cohort: brain cancer PMR = 234 (CI: 121,454), non-Hodgkin's lymphoma (NHL) PMR = 237 (CI: 137,410), prostate cancer PMR = 293 (CI: 187,460), and large intestine cancer PMR = 175 (CI: 125,245). The PMR for diseases of the nervous system was 202 (CI: 123,333). A similar pattern of elevated NHL, brain, and prostate cancer mortality along with excess deaths from diseases of the nervous system has been noted among other occupational cohorts exposed to pesticides.

Epidemiologic assessment of laboratory animal allergy among university employees.

The prevalence of, and risk factors for, laboratory animal allergy (LAA) among university employees were evaluated in a cross-sectional university-based study. A stratified random sample was drawn based on current or no laboratory animal exposure and smoking status. Participants received a modified ATS questionnaire; spirometry; methacholine challenge; and intradermal allergen skin tests. One hundred three currently animal-exposed and 113 never-occupationally-exposed employees participated. Controlling for smoking, currently exposed workers were significantly more likely than controls to describe work-related cough, odds ratio (O.R.) = 6.87; wheeze, O.R. = 12.96; and chest tightness, O.R. = 2.89. Skin test reactivity to non-animal antigens was associated in a dose-response fashion with both upper and lower respiratory symptoms, O.R. = 1.45 and 1.65, respectively, for each additional positive skin test. Exposed workers were significantly more likely than controls to react to methacholine at either 10 or 25 mg/ml, while controlling for smoking status, prior allergy, or asthma. Multiple logistic regression analysis revealed history of hay fever, family history of allergy, non-animal skin test positivity, animal bites, age, and smoking status to each be associated with work-related respiratory symptoms. These data suggest that atopy and smoking status are risk factors for LAA symptoms. Smoking was associated with work-related respiratory symptoms among animal-exposed workers, but not with skin test positivity. It is therefore recommended that periodic screening evaluations be performed on laboratory animal workers and that workers who are atopic, are smokers, or are symptomatic be placed in low exposure settings. These data further, support the need for efficient exhaust ventilation, personal protective clothing and, among high risk workers, the use of efficient respiratory protection.

An outbreak of naphthalene di-isocyanate-induced asthma in a plastics factory.

Seven cases of possible naphthalene di-isocyanate-related occupational asthma occurred in 1987 and 1988. These cases were reported to the National Institute for Occupational Safety and Health by personnel at a Midwest factory that manufactured plastic wheels for fork-lift trucks. The reporting of cases prompted (a) an evaluation of the workplace, including a medical screening of workers, to detect additional cases; and (b) an industrial-hygiene survey to determine the level of exposure to isocyanates.

Prospective evaluation of associations between hearing sensitivity and selected cardiovascular risk factors.

The prospective decline of hearing sensitivity was evaluated in an occupational cohort of university blue collar workers in relation to age, gender, occupational and nonoccupational noise exposure, smoking, blood pressure, and cholesterol. Each of these were associated with loss of hearing sensitivity univariately. When controlling for age and historical noise exposure in a multiple regression model, systolic blood pressure and cholesterol level were independently associated with decline in auditory sensitivity.

Pleural determinants of restrictive lung function and respiratory symptoms in an asbestos-exposed population.

To further define the relationship between asbestos-induced pleural fibrosis and restrictive lung function, we investigated the pleural determinants of respiratory symptoms and restrictive physiology in 1,211 sheet metal workers. We evaluated the relationship between specific components of pleural fibrosis (costophrenic angle involvement, diaphragmatic plaques, width and length of pleural fibrosis, pleural calcification, and the type of fibrosis-circumscribed plaque or diffuse pleural thickening) and both forced vital capacity and respiratory symptoms. We found that costophrenic angle involvement, the width and length of pleural fibrosis, and the presence of either circumscribed plaque or diffuse pleural thickening were each significantly associated with a lower FVC. No consistent relationship was observed between FVC and either diaphragmatic plaques or pleural calcification. However, since the pleural abnormalities were highly collinear, none of these abnormalities alone or in combination predicted the reduction in FVC significantly better than a model that included circumscribed plaques and diffuse pleural thickening. We also investigated the relationship of each component of pleural fibrosis with cough, dyspnea, and chest pain. After controlling for appropriate confounders, a trend toward significance was observed between increased width and length of fibrosis and dyspnea with exertion. Otherwise, these pleural abnormalities were not consistently related to any of the three respiratory symptoms. Our results indicate that although pleural plaques and diffuse pleural thickening and their components are independently associated with a lower FVC, these components of pleural fibrosis do not substantially improve the previously defined relationship between FVC and both circumscribed plaques and diffuse pleural thickening. In addition, a trend toward significance was observed between the width and length of the pleural abnormality and dyspnea while hurrying.

Acute respiratory fatality associated with exposure to sheet metal and cadmium fumes.

The authors report on a case of an acute fatality characterized by abdominal pain and respiratory failure occurring soon after beginning to weld and solder galvanized sheet metal. Heating of galvanized sheet metal is a recognized cause of metal fume fever, data from this patient suggests an additional and unrecognized risk for cadmium poisoning.

Leukemia incidence and radioactivity in drinking water in 59 Iowa towns.

Fifty-nine towns in Iowa with single source drinking water supplies were stratified on the basis of radium content in finished non-softened water to test the hypothesis of an association with total or acute myeloid leukemia. Fourteen towns had radium concentrations in drinking water exceeding the EPA safety limit of 5 picocuries per liter (pCi/L). A small increasing trend existed for total leukemia with increased radium content in drinking water that is in accordance with either the hypothesis of no effect or of a small effect.

Asbestos-induced pleural fibrosis and impaired lung function.

To assess the clinical significance of asbestos-induced pleural fibrosis, we evaluated the relationship between radiographic evidence of pleural fibrosis and spirometric values in 1,211 sheet metal workers. Of those with pleural fibrosis (n = 334), 78% had circumscribed plaques and 22% had diffuse pleural thickening involving the costophrenic angle. Factors that were found to be associated with the presence and type of pleural fibrosis included increased age (p less than 0.001), more years in the trade (p less than 0.0001), more years since first exposure to asbestos (p less than 0.0001), more pack-years of cigarette smoking (p less than 0.01), and the presence and degree of interstitial fibrosis (p less than 0.0001). After controlling for these potential confounders (age, years in the trade, latency, pack-years of smoking, and ILO profusion category), linear multivariate regression models demonstrated that both circumscribed plaques (p = 0.007) and diffuse pleural thickening (p = 0.008) were independently associated with decrements in FVC but not with decrements in the FEV1/FVC ratio. Furthermore, our data indicate that the effect of diffuse pleural thickening on decrements in FVC is approximately twice as great as that seen with circumscribed pleural plaques. We conclude that the presence and type of pleural fibrosis among asbestos-exposed workers is independently associated with a pattern of spirometry that is suggestive of an underlying restrictive defect in lung function.

Occupational disease surveillance data sources, 1985.

Health department epidemiologists in 50 states, New York City, and the District of Columbia were surveyed in 1985 about seven potential data sources for occupational disease surveillance. Reported sources of occupational disease data were: automated workers' compensation claims (63 per cent of the 52 respondents); provider reports (62 per cent); death certificates with occupation or industry (60 per cent); cancer registries with occupational histories (35 per cent); birth certificates with parent's occupation (27 per cent); non-cancer disease registries (13 per cent); and hospital or insurance records (8 per cent).