Weight of evidence for an association between adverse reproductive and developmental effects and exposure to disinfection by-products: a critical review.

Disinfection by-products (DBP) are a side effect of water chlorination. Some toxicological studies suggest an association between DBP exposure and adverse reproductive and developmental effects. This investigation considered all toxicological and epidemiological evidence for the various effects, outcome by outcome. The weight of evidence demonstrated that no association with DBP exposure exists for over a dozen outcomes including low and very low birth weight, preterm delivery, some specific congenital anomalies, and neonatal death. The analysis found inconsistent or very weak results for all congenital anomalies/birth defects, all central nervous system anomalies, neural tube defects, spontaneous abortion, and stillbirth. The weight of evidence suggested a positive association with DBP exposure for some measure of growth retardation (such as intrauterine growth retardation or small for gestational age) and for urinary tract anomalies. Having catalogued these effects, it should be noted that exposure assessment in the epidemiological studies published to date has been inadequate to definitively demonstrate an association of small magnitude. Exposure to DBP primarily has been based on routine (i.e., quarterly) monitoring of public water supplies for trihalomethanes (THM) matched to maternal residence. In order to determine whether an association exists between adverse reproductive and developmental effects and exposure to DBP, studies must consider the THM concentration and the quantity of the water actually consumed by pregnant women.

Pregnancy outcomes among U.S. Gulf War veterans: a population-based survey of 30,000 veterans.

PURPOSE: We evaluated an association between veterans' Gulf War service and reported adverse pregnancy outcomes. METHODS: We conducted a health survey in which selected reproductive outcomes of a population-based sample of 15,000 Gulf War veterans representing four military branches and three unit components (active, reserve, and National Guard) were compared to those of 15,000 non-Gulf veteran controls. RESULTS: Male Gulf veterans, compared with their non-Gulf veteran controls, reported a significantly higher rate of miscarriage (odds ratio [OR] = 1.62; 95% confidence interval [CI] = 1.32-1.99). Female Gulf veterans also reported more miscarriages than their respective controls, although their excess was not statistically significant (OR= 1.35; CI = 0.97-1.89). Both men and women deployed to the Gulf theater reported significant excesses of birth defects among their liveborn infants. These excess rates also extended to the subset of "moderate to severe" birth defects [males: OR= 1.78 (CI = 1.19-2.66); females: OR = 2.80 (CI = 1.26-6.25)]. No statistically significant differences by deployment status were found among men or women for stillbirths, pre-term deliveries or infant mortality. CONCLUSION: The risk of veterans reporting birth defects among their children was significantly associated with veteran's military service in the Gulf War. This observation needs to be confirmed by a review of medical records to rule out possible reporting bias.

US Army Chemical Corps Vietnam veterans health study: preliminary results.

The long-term health consequences of exposure to phenoxyherbicides used in Vietnam has been a great concern to the veterans. In addition to the Air Force Ranch Hand personnel, Army Chemical Corps personnel who served in Vietnam are thought to have had some of the highest herbicide exposures. The Department of Veterans Affairs commenced a study of veterans who served in Vietnam as members of the Army Chemical Corps and a comparison cohort of Army Chemical Corps personnel who served elsewhere. A total of 2872 Vietnam veterans and 2737 non-Vietnam veterans who served in the Army Chemical Corps were identified for inclusion in a telephone health interview survey with a random 20% sample of veterans receiving serum dioxin and other congeners assessments. In a feasibility study which included 284 Vietnam veterans and 281 non-Vietnam veterans, 100 serum assessments were conducted of which 95 were included in the analysis. Vietnam veterans with a history of spraying herbicides were found to have a statistically significant elevation in their current serum 2,3,7,8-TCDD concentrations compared to non-Vietnam veterans without a spray history (P = 0.05). Other 2,3,7,8-substituted dioxins levels were comparable to the levels found in the non-Vietnam veterans. This feasibility study demonstrated that serum dioxin concentrations from a sample of the study participants can be used to identify exposure variables in the health survey that can serve as a surrogate measure of phenoxyherbicide exposure.

Cancer incidence after childhood nasopharyngeal radium irradiation: a follow-up study in Washington County, Maryland.

A population from a hearing clinic in Washington County, Maryland, in 1943-1960 was followed to assess the risk of developing neoplasms from radium treatment of the nasopharynx for adenoid hypertrophy. Of the 2,925 subjects who attended the clinic, 904 received radium treatment. A nonconcurrent prospective study compared the cancer incidence among the irradiated persons with that among persons with other treatments. Seven brain tumor cases (three malignant and four benign) were identified in the irradiated group versus none in the nonirradiated group (relative risk = 14.8, 95% confidence interval: 0.76, 286.3). A nonsignificant excess risk of thyroid cancer was detected in the irradiated group based on two cases in the exposed group and one case in the nonexposed group (relative risk = 4.2, 95% confidence interval: 0.38, 46.6). Decreased risks of breast cancer, female genital cancers, and prostate cancer were observed among the irradiated individuals, although these deficits were not statistically significant individually. The decreased risk of sex hormone-related cancers in the irradiated group suggests possible radiation damage to the pituitary, with consequent reduction in pituitary hormone output and alterations in sexual and other hormonal development in early life. This hypothesis needs further evaluation.

Time trends in exposure measurements from OSHA compliance inspections of the pulp and paper industry.

Time trends in employee exposures to the air contaminants measured by the Occupational Safety and Health Administration (OSHA) during compliance inspections of pulp and paper manufacturing facilities conducted between 1979 and 1997 were evaluated based on the measurement results stored in the OSHA Integrated Management Information System (IMIS) database. The IMIS database is among the largest sources of occupational exposure measurements available for occupational health research in the United States. The IMIS database contains the results of 3,568 personal time-weighted average (TWA) measurements for 171 air contaminants made at 524 establishments in Standard Industrial Classification (SIC) 26. An analysis of these measurements revealed an overall decrease in the total number of measurements made per year since 1991, and a decrease in the percentage of measurements by year that exceeded the OSHA permissible exposure limits (PELs). Linear regression analyses detected decreasing trends in the geometric mean concentrations by year for 33 of the 36 agents analyzed.

Mortality among radiologic technologists in the united states (1926-1997). 2(nd) Follow up.

PURPOSE: To evaluate risk for all-cause and cause-specific mortality in a large, primarily female (73%) cohort of radiologic technologists.METHODS: The study consists of 145,915 radiation technologists, certified in the American Registry of Radiologic Technologists (1926-1982) and followed through 1997. Causes of death were obtained from death certificates or, more recently, through NDI Plus. Standardized Mortality Ratios (SMR) were computed and tests of homogeneity were performed to detect differences in mortality among causes. Poisson models were used to estimate risks using an internal comparison group.RESULTS: Significantly low SMRs were observed for all causes (0.76), all cancers (0.82), and diseases of circulatory system (0.69). Compared to U.S. women, the risk for breast cancer mortality bordered around unity (SMR 1.01, 95% CI 0.94-1.09). However, relative to all other cancers, breast cancer mortality was significantly increased (RSMR 1.24, p < 0.01). Elevated risk for breast cancer was associated with certification before 1940 (SMR 1.55, 95% CI 1.24-1.91), and duration of certification of 20-29 (SMR 1.21, 95% CI 1.06-1.37) and 30+ years (SMR 1.77, 95% CI 1.54-2.02). A 35% increase in leukemia risk was evident for women certified for a duration of 20-29 years and a 36% increase among women certified for 30+ years. Poisson analysis revealed a significant increase in breast cancer risk with increasing number of years certified among women first certified before 1940 (p < 0.001) and during 1940-49 (p = 0.05) compared to women first certified in 1950 or later.CONCLUSIONS: Preliminary findings of this study suggest increased breast cancer risk associated with occupational radiation exposures prior to 1950 and with long-term cumulative exposures. However, potential confounding by reproductive and other risk factors needs to be evaluated.

Carbonless copy paper and workplace safety: a review.

Carbonless copy paper (CCP), introduced in 1954, is ubiquitous in the U.S. marketplace, and because of this, many workers come into contact with it. Its safety to workers who handle large amounts of CCP has been addressed in numerous studies and reports; and the National Institute for Occupational Safety and Health (NIOSH) on two occasions has sought to determine what, if any, hazards to health CCP might pose. This review encompasses the world's literature on CCP and provides a weight-of-evidence analysis of the safety of CCP to workers in the United States. CCP is systematically studied on large groups of humans using repeat insult patch tests. Consistently, CCP in U.S. commerce since 1987 (the focus of this review) has produced neither primary skin irritation nor skin sensitization under exaggerated test conditions, demonstrating that no irritation or sensitization is expected on contact with CCP under normal conditions of manufacture and use. Years after the introduction of CCP, the first case reports appeared in 1974 suggesting an association between CCP use and various generic symptoms. Most of the earliest reports occurred in Sweden in response to negative publicity concerning the product, and to date approximately half of all published articles originate in Scandinavia. Many early reports were questionnaire/interview studies which suffered from suggestive questions, biases, and lack of control for confounding factors. Few studies included a comparison group (i.e., people not exposed to CCP) making it impossible to estimate risk values. Later, sick building syndrome studies, accounting for many relevant factors in the office environment, found no association between CCP exposure and symptoms unexplained by other factors. Animal studies showed that compounds used to manufacture CCP do not have acute toxic potential and are not genotoxic. Finally, very few published complaints have come from the manufacturing sector where the closest and most voluminous contact occurs. A few reports of symptoms have emanated from printing facilities (with a multiplicity of other chemical exposures), but generally most symptoms are reported in the office setting where the exposure is lower than in the manufacturing or printing settings. Based on the weight of the evidence, CCP currently in commerce in the United States is shown not to be the causative agent for the reported general symptoms sometimes associated with it over the years. Recently NIOSH evaluated the literature as to possible hazards to health posed by CCP, and NIOSH is anticipated to conclude that CCP is not a hazard to workers and has only a small possibility of producing mild and transient skin irritation.

Pregnancy outcomes among U.S. women Vietnam veterans.

BACKGROUND: Since the 1965-1975 Vietnam War, there has been persistent concern that women who served in the U.S. military in Vietnam may have experienced adverse pregnancy outcomes. METHODS: We compared self-reported pregnancy outcomes for 4,140 women Vietnam veterans with those of 4,140 contemporary women veterans who were not deployed to Vietnam. As a measure of association, we calculated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression adjusting for age at conception, race, education, military nursing status, smoking, drinking and other exposures during pregnancy. RESULTS: There was no statistically significant association between military service in Vietnam and index pregnancies resulting in miscarriage or stillbirth, low birth weight, pre-term delivery, or infant death. The risk of having children with "moderate-to-severe" birth defects was significantly elevated among Vietnam veterans (adjusted OR = 1.46, 95% CI = 1.06-2.02). CONCLUSIONS: The risk of birth defects among index children was significantly associated with mother's military service in Vietnam.

Mutagenic drinking water and risk of male esophageal cancer: a population-based case-control study.

Drinking mutagenic downstream water from the Huangpu River was hypothesized to have increased the risk for male esophageal cancer in Shanghai, China. The authors conducted a population-based case-control study of a total of 71 esophageal cancer deaths and 1,122 controls collected during a 5-year follow-up period, 1984-1988, from four male cohorts born before January 1, 1944, living in four communities consuming water with different mutagenicities in the Shanghai area. The controls represented a 1% random sample of the defined living cohorts selected at the end of each of the 5 years of follow-up. Logistic regression showed an odds ratio of 2.77 (95% confidence interval: 1.52, 5.03) for drinking mutagenic downstream water from the river versus drinking nonmutagenic upstream water after controlling for possible confounders including age, disease history (hepatitis, cirrhosis, schistosomiasis, digestive tract ulcer), hazardous occupational history, pesticide exposure, lifestyle factors (cigarette smoking, tea intake, and alcohol intake), dietary habits (intake of pickled vegetables, maize, peanuts, and cured meat), education, poverty, urban environment, and water chlorination.

Industry-wide study of mortality of pulp and paper mill workers.

A study of pulp and paper mill workers indicated low risks of death from all causes (standardized mortality ratio (SMR) = 0.74) and all cancers (SMR = 0.81) compared with U.S. rates. The leukemia death rate in workers was not higher than the U.S. rate but was higher than the rate in county populations surrounding mills. Workers whose last jobs were in the finishing areas of the mills had an elevated SMR for liver cancer. An internal comparison of occupational characteristics indicated that workers employed in mills using other chemical pulping operations had significantly elevated mortality from all causes, all cancers, heart disease, lymphomas, and brain cancers. Lung cancer mortality was elevated in mills using kraft pulping. The internal comparisons confirmed the association between work in finishing and the risk of liver cancer. This study was designed to investigate whether pulp and paper mill workers have any risks that would indicate the need for studies detailing exposures.

Lymphohematopoietic cancers and butadiene and styrene exposure in synthetic rubber manufacture.

The described nested case-control study of lymphohematopoietic cancers occurring in a cohort of synthetic rubber production workers was conducted to determine the associations of these cancers with exposure to butadiene and styrene. Cases have been confirmed through hospital record review of 95 percent of the cancers. Exposures are based on measured values of the two chemicals from personal monitoring data in seven of the eight plants under study. The results indicate that the risk of leukemia increases with exposure to a time-weighted average butadiene measure. The odds ratio at only 1 ppm average butadiene exposure is 1.50 (95% CI 1.07, 2.10). Work in specific areas also contributes to the risk, possibly because these areas have not been completely characterized for differences in butadiene exposure. Hodgkins disease is also associated with butadiene exposure. Multiple myeloma, lymphosarcoma, and all lymphomas are associated with exposure to styrene. Since workers in this industry are apparently exposed to two carcinogenic agents, further effort must be made to distinguish the exposures to each chemical over time and to characterize their interrelationship with the risk of cancers of the lymphohematopoietic system.

A follow-up study of childhood nasopharyngeal radium irradiation in Washington County, Maryland.

In 1978 an epidemiologic study exploring the health consequences of nasopharyngeal radium irradiation among individuals treated for adenoid enlargement in Washington County, Maryland, found an excess risk of brain tumors and a deficit of female breast cancers. The study population included all persons first seen at the Washington County Clinic for the Prevention of Deafness in Children from 1940 to January 1, 1960. We will continue the follow-up of irradiated and nonirradiated patients to (1) assess the risk of brain tumors and other neoplasms of the head and neck developing during a 40-year period, (2) assess hormone-related disorders resulting from irradiation of the pituitary gland, and (3) compare cancer incidence and mortality rates among exposed and nonexposed groups. Of the 2135 persons eligible for this study, 93.5% have been traced, and 90% have replied to a mailed questionnaire that elicits information on demographic characteristics, reproductive and medical history, infertility, and other sources of radiation exposure. Information on cancer incidence and mortality is being obtained from the Washington County Cancer Registry and death certificate files from Washington County and the Social Security Administration. Statistical methods to be used in the data analysis include standardized mortality ratios, standardized cancer incidence ratios, and Kaplan-Meier survival analysis.

Characteristics of nonsmoking women in NHANES I and NHANES I epidemiologic follow-up study with exposure to spouses who smoke.

Few studies have examined the relation between passive smoking and dietary intake in a large population. This report examines the nutrition and behavioral characteristics of 3,896 nonsmoking women from the first National Health and Nutrition Examination Survey (NHANES I) population in relation to exposure to environmental tobacco smoke. The data indicate that nonsmoking women who were exposed to husbands who smoked were more likely to be older, have lower education, live in the city, and have other health behaviors that could increase their risk of lung cancer compared with nonsmoking women with husbands who did not smoke. The nonexposed women were more likely to take vitamin supplements, to not drink alcohol, and to consume higher levels of dietary vitamin A, vitamin C, and calcium. The exposed and nonexposed women showed no difference in the levels of fatty acid intake nor in the levels of several other foods from the food frequency list after correction for age. Many of the differences that the authors observed between the women who were exposed and nonexposed to passive smoking could affect the risk of cancer. Therefore, they recommend that future studies of nonsmokers examine the influence of both passive smoking and diet on the risk of disease rather than examine the influence of a single factor.