Hemoglobin adducts and sister chromatid exchanges in hospital workers exposed to ethylene oxide: effects of glutathione S-transferase T1 and M1 genotypes.

Ethylene oxide (EtO) is a genotoxic carcinogen with widespread uses as an industrial chemical intermediate and sterilant. We examined the effects of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) genotypes on the levels of N-(2-hydroxyethyl)valine (HEV) adducts in the erythrocytes and sister chromatid exchange (SCE) in lymphocytes from a group of 58 operators of sterilizers that used EtO and nonexposed workers from nine hospitals in the United States and one hospital in Mexico City. Cumulative exposure to EtO was estimated during the 4-month period before the collection of blood samples. Results showed that EtO exposure was significantly associated with the levels of HEV adducts and SCE after adjusting for cigarette smoking and other potential confounders. A significantly higher HEV adduct level (0.17 +/- 0.03 versus 0.08 +/- 0.01, mean +/- SE; P = 0.02) but lower SCE frequency (5.31 +/- 0.39 versus 6.21 +/- 0.17; P = 0.04) was observed in subjects with homozygous deletion of the GSTT1 gene (null genotype) as compared with those with at least one copy of the gene (positive genotype). In multiple regression analysis, the GSTT1-null genotype was associated with an increase in HEV adduct level (beta = 1.62; P = 0.02) and a decrease in SCE frequency (beta = -1.25; P = 0.003) after adjusting for age, gender, race, education, cigarette smoking, and EtO exposure status. The inverse SCE-GSTT1 relationship remained unchanged when SCE was further examined in relation to HEV adducts as an indicator of the internal EtO dose. The GSTM1 genotype was not associated with the level of either HEV adduct or SCE. These data indicate that the GSTT1-null genotype is associated with increased formation of EtO-hemoglobin adducts in relation to occupational EtO exposure, suggesting that individuals with homozygous deletion of the GSTT1 gene may be more susceptible to the genotoxic effects of ETO: The unexpected finding of decreased SCEs, which is less clear, may be attributed to the nonchemical specificity of this end point and the lack of expression of the GSTT1 enzyme in lymphocytes.

Spontaneous abortion, sex ratio, and paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

There is conflicting research regarding an association between fetal death and paternal exposure to Agent Orange, a phenoxy herbicide widely used in Vietnam that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Men who worked in the U.S. factories that produced Agent Orange were exposed to TCDD at levels hundreds of times higher than TCDD levels in the general population. Wives of TCDD-exposed chemical workers and wives of nonexposed neighborhood referents were interviewed to determine reproductive history. Paternal serum TCDD level at time of conception was estimated for each pregnancy using serum samples taken in 1987. Estimated TCDD levels of workers during or after exposure were high (median, 254 ppt; range, 3-16,340 ppt) compared to referent levels (median, 6 ppt; range, 2-19 ppt). No association between paternal TCDD level at the time of conception and spontaneous abortion was observed among pregnancies fathered by workers with TCDD levels of < 20 ppt [odds ratio (OR) = 0.77; 95% confidence interval (CI), 0.48-1.22], 20 to < 255 ppt (OR = 0.81; 95% CI, 0.40-1.63), 255 to < 1,120, (OR = 0.69; 95% CI, 0.30-1.58), and >or= 1,120 ppt (OR = 0.95; 95% CI, 0.42-2.17) compared to pregnancies fathered by referents. The sex ratio [males/(males + females)] of offspring also did not differ by TCDD exposure (0.53 and 0.54 among workers and referents, respectively). We did not find an association between paternal serum TCDD level and spontaneous abortion or sex ratio of offspring in this population. The estimated TCDD levels in this exposed worker population were much higher than in other studies, providing additional evidence that paternal TCDD exposure does not increase the risk of spontaneous abortion at levels above those observed in the general population. The study could not evaluate the effect of father's childhood or prenatal TCDD exposure on subsequent sex ratio.

Knowledge of medical history information among proxy respondents for deceased study subjects.

Proxy respondents were interviewed for 96 decedents in an occupational cohort. A second respondent was interviewed for 59 decedents. Medical records were reviewed to validate questionnaire information. The percentage of respondents who answered "don't know" (non-response) to questions about medical condition ranged from 5% (cancer and heart disease) to 17% (ulcers). Non-response rates were lowest among spouses, intermediate among children, parents, and siblings, and highest among other relatives and friends. Among 41-55 pairs, depending on the condition, agreement between paired respondents was excellent (kappa > 0.75) for ulcers, cancer, diabetes, and lung disease. A higher percentage of medical records was obtained for decedents with spouse respondents and for decedents with more recent dates of death. Sixty percent or more of the medical records were obtained for patients with cancer (n = 30), heart disease (n = 26), stroke (n = 9), and liver disease (n = 10). The positive predictive value of the proxy respondent information for these conditions was 93, 81, 78, and 60%, respectively.

Obstacles and opportunities in designing cancer control communication research for farmworkers on the Delmarva Peninsula.

Little is known about the incidence of cancer among farmworker populations or about effective strategies for communicating with farmworkers about cancer prevention. Some studies suggest that farmworkers may have unusually high incidences of skin and cervical cancers. With these two cancers as the focus, a group of interviewers, researchers, and health communication specialists set out to create, implement, and evaluate a cancer control demonstration project geared toward farmworkers. In 1994, a situation analysis was conducted to identify constraints and opportunities for providing farmworkers with cancer control information and services. The situation analysis provided valuable information to aid in developing intervention and evaluation strategies. This paper outlines how and why the situation analysis was conducted and what was learned with regard to the farmworker population on the Delmarva Peninsula. Living conditions and the local availability of cancer control services are described. Obstacles to conducting research and interventions with farmworkers are highlighted. Based on what was learned, recommendations are made for designing cancer control research and intervention for farmworkers.

The Upper Midwest Health Study: a case-control study of primary intracranial gliomas in farm and rural residents.

Since several studies indicated that farmers and agricultural workers had an excess risk of brain cancer, the National Institute for Occupational Safety and Health initiated the Upper Midwest Health Study to examine risk of intracranial glioma in the non-metropolitan population. This population-based, case-control study evaluated associations between gliomas and rural and farm exposures among adults (ages 18 to 80) in four upper midwestern states (Iowa, Michigan, Minnesota, Wisconsin). At diagnosis/selection, participants lived in non-metropolitan counties where the largest population center had fewer than 250,000 residents. Cases were diagnosed 1 January 1995 through 31 January 1997. Over 90% of 873 eligible ascertained cases and over 70% of 1670 eligible controls consented to participate. Participants and nonparticipants, evaluated for "critical questions" on main and refusant questionnaires, differed significantly in farming and occupational experience, ethnicity, education, and lifestyle. The 1,175 controls were more likely than the 798 cases to have reported ever drinking alcohol (77% vs. 73%, adjusted odds ratio (OR) 0. 73, 95% confidence interval (CI) 0.59-0.92) and having had panoramic dental x-rays (34% vs. 29%, OR 0. 75, CI 0.61-0.92). Controls spent a greater percentage of their lives in non-metropolitan counties (78% vs. 75%, OR 0.81, CI 0.67-1.09). Among ever-farmers, controls were more likely to have had exposure to farm insecticides (57% vs. 50%, OR 0.75, CI 0.59-0.95) and farm animals (96% vs. 91%, OR 0.48, CI 0.25-0.90). Moving to a farm as an adolescent (ages 11 to 20) vs. as an adult was associated with a greater risk of glioma. In our study sample, farm or rural residence and summary farm exposures were associated with decreased glioma risk. However, nonparticipation by never-farming eligible controls could have affected results. Comparisons of farm chemical exposures may clarify associations between farming and glioma that others have reported.

Intervention research: science, skills, and strategies.

Despite a rich history of etiological research, the field of occupational safety and health does not have a rigorous history of research on what works and does not work to prevent and control occupational diseases and injuries. National and global transformations of economies and workplaces with enhanced competitiveness require more attention to options for interventions. A three-pronged approach to building a body of knowledge on intervention research in occupational health and safety is identified in this paper. The approach focuses on the science, skills, and strategies that can be useful in intervention research. Scientifically, researchers can draw on constructs and techniques from epidemiology, evaluation practice, and clinical trials. Experimental and nonexperimental approaches have value for occupational studies. The skills needed represent a range of disciplines beyond those traditional of health and safety; social scientists, economists, and organizational theorists often need to be part of research teams. Strategic approaches involve more labor-management partnerships, prospective study designs, and the use of intermediate and surrogate indicators. The strategic challenge will be to conduct intervention research against a backdrop of overriding political and economic pressures.

Peripheral neuropathy after occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Reports of human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) describe signs and symptoms consistent with exposure-related peripheral neuropathy. In a cross-sectional study, prevalence of peripheral neuropathy was measured in 265 workers exposed 15 years earlier to chemicals contaminated with TCDD and in 244 unexposed, age-, race-, gender- and community-matched comparisons. Cases of peripheral neuropathy were defined from examination, electrophysiologic and quantitative sensory tests, and symptoms. Exposure was assessed by measuring lipid-adjusted serum TCDD levels. The mean serum TCDD level for workers (220 parts per trillion (ppt)) was significantly higher than for referents (7 ppt) (p < .0001). Thirty-two percent of both worker and referent groups met the case definition for peripheral neuropathy. In the logistic regression analyses, serum TCDD level was not related to peripheral neuropathy. These data suggest that despite continued high serum TCDD levels, peripheral neuropathy is not a long-term sequela of high exposure to TCDD-contaminated chemicals. However, the study cannot preclude the occurrence and subsequent resolution of acute effects caused by high exposure, as experienced in Seveso and possibly by some workers, while exposed to high levels of TCDD-contaminated substances.

Methodologic issues in risk communications to workers.

Until the late 1980s, epidemiologists in general did not individually notify subjects of the results of epidemiological studies. Now that they are beginning to do so, the question arises of how best to notify those involved. In general, the methods, the processes and the policies related to effectively communicating risks to workers have not been thoroughly examined in the scientific literature. This is especially true in situations where workers have already experienced the exposures that led to increased risks for disease. The recent increasing numbers of notifications have raised several methodologic issues, which are examined in terms of: (1) the content of notification, (2) the process of notification, and (3) the evaluation of the impact and effectiveness of notification. Too often in the discussion concerning notification, attention is paid to the content but the process and evaluation are rarely considered. The potential impact and effectiveness of notification have been raised as reasons for or against notification, but rarely has there been a concerted effort to evaluate a notification in this regard. This workshop was designed to address all these issues. The ultimate goal is to improve communications for workers.