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.

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.

Exposure to environmental tobacco smoke in the workplace and the impact of away-from-work exposure.

Concentrating on exposure in workplaces where smoking occurs, we examined environmental tobacco smoke (ETS)-related concentration data from the 16-City Study. This study involved a large population of nonsmokers, used personal monitors, and encompassed a wide selection of ETS-related constituents. This first article in a series of three describes the 16-City Study, considers the impact of demographic variables, and concludes that these variables did not explain differences in exposure to ETS. We compared 16-City Study concentrations obtained in the workplace to previously reported workplace concentrations and determined that data from this study were representative of current ETS exposure in nonmanufacturing workplaces where smoking occurs. Considering factors other than demographic factors, we found that, not surprisingly, the number of cigarettes observed in the workplace had an impact on exposure concentrations. Finally, we compared people from homes where smoking occurs with people from nonsmoking homes and found that people from smoking homes observed more smoking in the workplace and experienced higher concentrations of ETS-related compounds in the workplace, even when they observed the same number of cigarettes being smoked in the workplace. In two subsequent articles in this series, we discuss relationships between various ETS markers and provide estimates of distributions of doses to nonsmoking workers employed in workplaces where smoking occurs.

Use of environmental tobacco smoke constituents as markers for exposure.

The 16-City Study analyzed for gas-phase environmental tobacco smoke (ETS) constituents (nicotine, 3-ethenyl pyridine [3-EP], and myosmine) and for particulate-phase constituents (respirable particulate matter [RSP], ultraviolet-absorbing particulate matter [UVPM], fluorescing particulate matter [FPM], scopoletin, and solanesol). In this second of three articles, we discuss the merits of each constituent as a marker for ETS and report pair-wise comparisons of the markers. Neither nicotine nor UVPM were good predictors for RSP. However, nicotine and UVPM were good qualitative predictors of each other. Nicotine was correlated with other gas-phase constituents. Comparisons between UVPM and other particulate-phase constituents were performed. Its relation with FPM was excellent, with UVPM approximately 1 1/2 times FPM. The correlation between UVPM and solanesol was good, but the relationship between the two was not linear. The relation between UVPM and scopoletin was not good, largely because of noise in the scopoletin measures around its limit of detection. We considered the relation between nicotine and saliva continine, a metabolite of nicotine. The two were highly correlated on the group level. That is, for each cell (smoking home and work, smoking home but nonsmoking work, and so forth), there was high correlation between average continine and 24-hour time-weighted average (TWA) nicotine concentrations. However, on the individual level, the correlations, although significant, were not biologically meaningful. A consideration of cotinine and nicotine or 3-EP on a subset of the study whose only exposure to ETS was exclusively at work or exclusively at home showed that home exposure was a more important source of ETS than work exposure.

Distribution of exposure concentrations and doses for constituents of environmental tobacco smoke.

The ultimate goal of the research reported in this series of three articles is to derive distributions of doses of selected environmental tobacco smoke (ETS)-related chemicals for nonsmoking workers. This analysis uses data from the 16-City Study collected with personal monitors over the course of one workday in workplaces where smoking occurred. In this article, we describe distributions of ETS chemical concentrations and the characteristics of those distributions (e.g., whether the distribution was log normal for a given constituent) for the workplace exposure. Next, we present population parameters relevant for estimating dose distributions and the methods used for estimating those dose distributions. Finally, we derive distributions of doses of selected ETS-related constituents obtained in the workplace for people in smoking work environments. Estimating dose distributions provided information beyond the usual point estimate of dose and showed that the preponderance of individuals exposed to ETS in the workplace were exposed at the low end of the dose distribution curve. The results of this analysis include estimations of hourly maxima and time-weighted average (TWA) doses of nicotine from workplace exposures to ETS (extrapolated from 1 day to 1 week) and doses derived from modeled lung burdens of ultraviolet-absorbing particulate matter (UVPM) and solanesol resulting from workplace exposures to ETS (extrapolated from 1 day to 1 year).

Food intake and mortality in the United States.

Patterns of food intake and cause-specific death rates were compared for population groups of the United States for 1965, the first year for which national files are available. Aging was a much more important determinant of death rates than type of food eaten. There were no strong patterns of rank correlations of food intake and cause of death, but there was a preponderance of positive rank correlations for alcohol. This, together with similarities of age distributions of alcohol intake and death rates for causes related to alcohol, suggested the hypothesis that alcohol was associated with increased mortality. Other than this, because of the limited power of the exploratory statistical procedures applied, the hypothesis that there were health differences in people eating different foods could be neither accepted nor rejected.

Psychosocial factors and blood pressure.

Blood pressure levels as recorded in a community-wide screening programme were compared with findings in an earlier mental health study for persons who participated in both programmes. Blood pressure was not related to previously ascertained psychosocial characteristics among persons who were not under treatment for hypertension, suggesting that depression, hostility, psychosomatic reactions to stress, or the felt need for help with emotional problems were not important in the pathogenesis of hypertension. Treatment for hypertension, however, was associated with an excess of psychosomatic symptoms, a factor which needs to be taken into account in assessing the benefits of treatment.

Is ABH nonsecretor status a risk factor for obstructive lung disease?

In a multidisciplinary study of risk factors for chronic obstructive pulmonary disease (COPD), a significantly more impairment of forced expiration was observed in ABH nonsecretors than in ABH secretors among 1017 white adults. (ABH refers to the "A" and "B" antigens of the ABO blood group system and "H", the heterogenetic substance which is found in persons of all ABO types including type "O".) Nonsecretors had significantly lower mean values of forced expiratory volume in one second as a percentage of forced vital capacity (FEV1/FVC%) and a significantly larger proportion of them had aberrant values, defined as FEV1/FVC% less than 68. These differences remained when mean values or rates of aberrancy were adjusted for other factors reported to alter risk of airway obstruction. In view of the known COPD-peptic ulcer and nonsecretor-duodenal ulcer associations, these findings suggest that the ability to secrete ABH antigens into secretions of the respiratory and gastrointestinal tract may have a protective effect on epithelialized organs in general, or on the lung and portions of the gut specifically.

Patterns of forced expiratory flows in groups at risk for chronic obstructive pulmonary disease.

In a modified case-control study of obstructive pulmonary disease (COPD), airways obstruction has been found to be associated with age, sex, protease inhibitor type, socioeconomic status (SES) and smoking. In this paper patterns of forced expiratory flows are examined in persons demonstrating various risk factors. Two broad patterns of flow limitation emerge. The first pattern, characterized by lower flows at high lung volumes, is found in first-degree relatives of patients with COPD and subjects with a low SES. This pattern, consistent dysfunction of large airways, may reflect reversible decreases of airway caliber. The second pattern, characterized by lower flows at low lung volumes, is found in older subjects. This pattern, consistent with nonhomogeneously emptying lungs or dysfunction of small airways, may reflect more chronic irreversible changes. Smokers and male subjects exhibit both patterns of flow limitation when compared with subjects who had never smoked and female subjects. It is possible that the combination of the patterns reflects a particularly high risk for the development of COPD in male smokers.

Alcohol consumption and airway obstruction.

To clarify the basis of the reported association between alcohol and pulmonary disease, the relationship between intake of alcohol and pulmonary function was examined in 2,539 community-dwelling adult participants in an ongoing longitudinal study of risk factors for airway obstruction. Forced expiratory volume in 1 s, expressed as a percentage of forced vital capacity, was used as the indicator of airway obstruction, and forced vital capacity expressed as a percentage of the predicted value was used as an index of restriction. Although crude (unadjusted) mean values of the ratio of forced expiratory volume in 1 s to forced vital capacity were significantly lower for heavy than for light drinkers, the difference disappeared when adjustment was made for numerous confounding factors (including such recognized risk factors for pulmonary disease as cigarette smoking, low socioeconomic status, male sex, and age). There was also no evidence of an association between consumption of alcohol and airway restriction. Although these findings do not rule out a possible effect of alcohol on pulmonary disease, its impact, if any, is probably the result of interaction with other factors associated with alcoholism, if not derived primarily from those other factors.

A common familial component in lung cancer and chronic obstructive pulmonary disease.

First-degree relatives of lung-cancer patients and of patients with chronic obstructive pulmonary disease had significantly higher age-sex-race-smoking-adjusted rates of impaired forced expiration than first-degree relatives of patients with non-pulmonary disease or community-derived comparison series (neighbourhood controls and teachers). Subclassification of the data and multiple adjustment for smoking, race, sex, and other confounding factors emphasised the consistency of the pattern. These findings strongly suggest that lung cancer and chronic obstructive pulmonary disease share a common familial component other than smoking. The clinical manifestation may depend on the presence of one or more other cofactors as yet undefined.