Review of health consequences from high-, intermediate- and low-level exposure to organophosphorus nerve agents.

Short and long-term health effects from exposure to organophosphorus (OP) military and insecticidal nerve agents are evaluated based on the abundant scientific literature published over five decades on health effects in humans (from human experimentation and occupational exposures) and in laboratory animals. Four distinct health effects are identified: acute cholinergic toxicity; organophosphate-induced delayed neuropathy (OPIDN); subtle long-term neuropsychological and neurophysiological effects; and a reversible muscular weakness called 'intermediate syndrome'. Some effects are subtle and difficult to differentiate from health effects caused by other diseases or occupational exposures. Each effect has data suggesting threshold exposure levels below which it is unlikely to be clinically detectable. Therefore, meaningful interpretation of human and animal studies requires rigid exposure characterization. Because precise exposure levels are often difficult to reconstruct, a system for characterizing exposure is proposed based upon observed initial acute signs and symptoms, as high-level (definitive cholinergic poisoning); intermediate-level (threshold cholinergic effects including miosis, rhinorrhea or clinically measurable depression of cholinesterase); and low-level (no immediate clinical signs or symptoms) exposure. Threshold exposure levels for known long-term effects from OP nerve agent are at or above intermediate-level exposure. Long-term health effects seen at intermediate-level exposures or in many survivors of high-level exposure are subtle, detectable in exposed populations but not individuals, and not reported in individuals experiencing low-level exposure alone. Co-exposure to other pharmaceutical agents may promote or protect against health effects from OP nerve agents, but qualitatively they are the same effects seen with OP nerve agents alone. Thus, the system for characterizing exposure based on initial acute effects is also useful for evaluating health outcomes from co-exposure to OP nerve and other agents.

Polychlorinated biphenyl (PCB) and dichlorodiphenyl dichloroethylene (DDE) exposure among Native American men from contaminated Great Lakes fish and wildlife.

The New York State Department of Health is performing an investigation of Mohawk men, women, and infants who live at the Akwesasne Reserve along the St. Lawrence River in New York, Ontario, and Quebec Three large industrial facilities bordering the Akwesasne Reserve have seriously contaminated the soil and the sediments and fish of the adjacent St. Lawrence River with polychlorinated biphenyls (PCBs). The main study goals are to investigate the associations among the consumption of locally caught fish, residential exposure, body burdens of PCBs, and liver enzyme induction. Contamination with PCBs, polychlorinated dibenzofurans, polychlorinated dibenzodioxins, polyaromatic hydrocarbons, dichlorodiphenyl dichloroethylene (DDE) and other chemicals has been documented in locally caught fish, ducks, and other wildlife. The contamination of fish and wildlife is a major concern of the Mohawk people, since their tradition and culture emphasize the interdependence of man and his environment and because many residents formerly depended heavily on local fish and waterfowl for food. The focus of this research from 1986-1992 was on nursing women and infants. The major purpose of the current project is to determine if there are associations between dietary, residential, and occupational exposures to PCBs and DDE and individual body burdens in Mohawk men, specifically the husbands, partners, fathers, brothers, or other male relatives of the women in our other studies. In other fish-eating populations, adult men have tended to demonstrate higher PCB and DDE body burdens than women and children. Exposure estimates based on the reported consumption of locally caught fish and wildlife and residential histories will be correlated with the specific pattern of PCB congeners found in serum, thereby establishing a direct relationship between two potential sources of exposure and body burdens. Liver function will be examined through the caffeine breath test (CBT), a sensitive, noninvasive method of assessment of enzyme induction, one of the earliest detectable biological responses to PCBs in laboratory animals. This test appears promising as a method to detect subtle subclinical effects before the onset of overt clinical symptoms. The project is among the first to explore differences in dietary and other exposures, body burdens, and potential adverse health effects due to specific PCB congeners in men and women from the same source population.

Fish PCB concentrations and consumption patterns among Mohawk women at Akwesasne.

A study was conducted to determine concentrations of polychlorinated biphenyls (PCBs) in local fish and to establish patterns of fish consumption of nursing Mohawk women residing near three industrial hazardous waste sites. From 1986 to 1992, 97 Mohawk women were interviewed within one month postpartum. A comparison group consisted of 154 nursing Caucasians. Samples of 348 local fish were analyzed for PCBs. The results indicated that fish in the Mohawk area, especially those collected offshore from the waste sites, had been contaminated with PCBs. The dietary data showed a greater past prevalence of local fish consumption among Mohawk mothers, with an overall annual mean of 23.5 local fish meals more than one year before the pregnancy compared with 14.1 for the control women (p < 0.001). The prevalence of consumption by the Mohawks, however, declined over time, resulting in overall mean rates of 9.2 local fish meals one year or less before pregnancy, and 3.9 meals per year during pregnancy (p < 0.001 for linear trend). Compared to the Mohawks, significantly fewer control women stopped eating local fish, and their rates declined less sharply. A secular trend was also observed in the overall rate of consumption during pregnancy for the Mohawks, with those who gave birth in 1986-1989 having a mean of 10.7 local fish meals per year during pregnancy, compared with means of 3.6 and 0.9 respectively for women who delivered in 1990 and 1991-1992 (p < 0.05 for linear trend). No such trend was apparent for the controls. No background variable was significantly related to the rate of local fish consumption among the Mohawks, but a decrease over time in the rate of local fish consumption was greater among those Mohawks who ate the most local fish initially (r = -0.76, p < 0.001), or who also reduced their alcohol intake during pregnancy (r = 0.35, p < 0.05). Mohawks were also more likely than the controls to trim the fat, remove the skin from, and fry and fish they ate during the past year. These dietary changes may be the result of advisories that have been issued over the past decade recommending against the consumption of local fish by pregnant and nursing Mohawk women. Such changes, if sustained, should reduce their exposure to PCBs and correspondingly the potential for adverse health effects.

Risk factors for developing eosinophilia myalgia syndrome among L-tryptophan users in New York.

Using a case-control study design, patients with eosinophilia myalgia syndrome (EMS) who had used L-tryptophan (LT) were compared with LT users who did not develop EMS. Of the 113 case patients and 95 controls who had used a retail brand that could be traced to a bulk LT producer, all (100%) case-patients and 69 (73%) controls used LT brands that were traced to Showa Denko K.K. (lower 95% CL = 10.0). Among the users of LT produced by Showa Denko K.K., the risk of EMS was greater for persons who used LT produced after December 1, 1988 (OR = 25.8, [95% CL = 7.1, 101.4]). The risk of developing EMS increased with increased dosage of LT, increased age, and use of LT as a sleeping aid. These epidemiologic data support the hypothesis that the etiologic agent in EMS is a contaminant introduced into LT products during production.

Occupational mercury exposure and male reproductive health.

This retrospective cohort study was designed to investigate the relationship of male occupational exposure to elemental mercury and several reproductive outcomes. All subjects worked at least 4 months between 1953 and 1966 at a plant that used elemental mercury; 247 white male employees who had the highest exposures were compared to 255 matched nonexposed employees. Individual exposure to mercury was estimated from urinary mercury measurement records. Information on reproductive history and potential confounding variables was obtained through personal interview with each of the employees and with a subset of their wives. No associations were demonstrated between mercury exposure and decreased fertility or increased rates of major malformations or serious childhood illnesses. After controlling for previous miscarriage history, mercury exposure was not a significant risk factor for miscarriage. Because of this study's potential problems with long-term recall, further studies of the effect of mercury on pregnancy outcome are warranted in other populations.

The influence of work on the outcome of low-risk pregnancies.

In this study, the relation of white-collar work on the outcomes of low-risk pregnancies was investigated. The medical records of 300 primiparous women whose pregnancy outcomes were known were selected sequentially from prenatal care log books over a 6-month period in three private, group obstetric practices in a university community. The majority of these women worked outside the home and included 220 white-collar workers (73 percent) and 28 blue-collar workers (9 percent). Thirty-four women (11 percent) were homemakers. Within this sample, 197 women (66 percent) met the selection criteria for low-risk pregnancies based on known sociodemographic, medical, and health risk factors. Although the sample numbers were small, comparison of low-risk white-collar workers (n = 141) with low-risk homemakers (n = 24) showed significant differences for rates of Cesarean section for failure to progress (16 percent versus 0 percent, P less than 0.05) and a summary index of poor delivery and/or infant outcome (21 percent versus 4 percent, P less than 0.05). No other adverse outcomes were significantly associated with occupation. This study suggests that increased pregnancy risks may be associated with white-collar work in otherwise low-risk women.