A pilot epidemiologic study of possible health effects associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin contaminations in Missouri.

In 1971, 2,3,7,8-tetrachlorodibenzodioxin (TCDD)-containing waste oils were sprayed for dust control on residential, recreational, and work areas in Missouri. In several of these areas, the magnitude and the extent of this environmental contamination were not known until late 1982 or 1983. In the first phase of the investigation, a group of persons considered to be at highest risk of exposure and an appropriate comparison group were selected from reviews of Health Effects Survey screening questionnaires. These persons received complete medical examinations and a series of laboratory tests focused on detecting presymptomatic effects in key target organ systems (i.e., hepatic, dermatologic, immunologic, and neurologic effects). Comparisons of these two groups did not produce any firm indications of increased disease prevalence directly related to the putative exposures; of significance is the fact that no cases of chloracne or porphyria cutanea tarda were seen. Nevertheless, no overall definitive conclusion should be based just on this initial pilot study. Insights were provided that are being examined in more refined epidemiologic studies using different designs and strategies--especially of larger, more homogeneous population groups in which exposure status can be better characterized--focused primarily on discerning any potential effects on the urinary tract, liver, neurological, and immune systems. Concurrently, research into the development of replicable laboratory analytical methods and reference ranges for measuring TCDD body burden are being pursued.

Effects of polychlorinated biphenyls and lipemia on serum analytes.

Twelve serum analytes [triglycerides, cholesterol, total and conjugated bilirubin, high-density-lipoprotein cholesterol (HDL-C), alkaline phosphatase (AP), gammaglutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), beta-glucuronidase (beta-glu), alanine aminopeptidase (AAP), and 5'-nucleotidase (5'nuc)] were measured to investigate their correlation with exposure to polychlorinated biphenyls (PCBs) and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT). The relationship between serum lipids, lipophilic toxicants, and the analytes was also evaluated. The beta-glu, 5'nuc, triglycerides, cholesterol, and total bilirubin correlated positively and significantly with log concentrations of serum total PCBs and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a metabolite of DDT. The more highly chlorinated PCBs (Aroclor 1260) had significant, positive correlations with several serum analytes, but the less chlorinated PCBs (Aroclor 1242) correlated significantly and negatively only with HDL-cholesterol. Triglyceride- and cholesterol-rich lipoproteins were added to serum to determine the effects of lipids on these assays. Several were spuriously elevated. AP and beta-glu were not affected by lipoprotein addition with the methods used in this study. AAP was increased significantly only at triglyceride concentrations exceeding 400 mg/dl. Lipoproteins may be elevated because of deranged lipid metabolism in response to PCBs, or PCBs may be elevated because elevated lipoproteins are present, as in familial triglyceridemia, a relatively common dyslipoproteinemia. Because this relationship is not well understood with respect to cause and effect, we propose the further use in epidemiological investigations of assay methods that are little affected by blood lipids yet are correlated with PCB concentrations. Congener-specific quantification of PCBs would help elucidate the effects of PCBs on assays used to monitor health effects.

A case-control study of stomach cancer in a coal mining region of Pennsylvania.

Historically coal mining populations have been reported to have elevated stomach cancer incidence rates. To identify which factors might be associated with cases who reside in these high risk areas, and specifically if particulate exposures from coal mining and coal utilization are associated with risk, a mining area of western Pennsylvania was defined for a retrospective case-control study. One hundred seventy-eight resident cases, identified from certificates of death, were compared to three controls: digestive cancer deaths, arteriosclerotic heart disease deaths, and neighborhood (living) controls. Controls were matched to each case on age, race, sex, and residence. Interviews were conducted during 1981 and 1982. Excess risks were shown for foreign born and eastern Europeans. Coal mining was not shown to be a risk factor for males, while an association was seen for female cases whose husbands were miners. Farming was a risk factor for males and females. Marked decreased risks were shown for gas heating and cooking fuels, with elevated risks for coal, wood and oil heating fuels, and wood cooking fuel. These findings are associated with lower socioeconomic status, and suggest environmental exposures or lifestyles that are directly and indirectly related to these risks factors. The marked inverse relationship between stomach cancer and use of gas heating and cooking fuel may be of important etiologic significance, especially in association with dietary changes. Further evaluation of prior use of various types of heating and cooking fuels needs to be considered especially using incident rather than case deaths.

The public health response to 2,3,7,8-TCDD environmental contamination in Missouri.

In 1971, waste oil containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was sprayed for dust control on a number of residential, recreational, and work areas in Missouri. In several of them, the level and extent of environmental contamination were not known until late 1982 or 1983. Extrapolation from existing toxicological data indicated the potential for substantial adverse health effects in highly exposed populations. As a result, the Missouri Division of Health and the Centers for Disease Control initiated close collaboration with the Environmental Protection Agency (EPA) on review and evaluation of environmental data, the development of health advisories to EPA on the need for remedial or preventive actions at specific contaminated sites, a health education effort for the medical community and general public, establishment of a dermatological screening clinic, establishment of a central listing of potentially exposed persons through administration of a health effects survey questionnaire, and a pilot medical study of a "highest risk" cohort. Strategies for additional interventions will continue to be based on findings derived from this first phase of the investigation.

Dietary vitamin A deficiencies and stomach cancer.

The hypothesis of vitamin A intake deficiencies serving as an antecedent factor in the development of stomach cancer was assessed employing a case-control design. Interviews of proxy informants for 111 cases and a pair-matched control group were conducted using a food frequency questionnaire from which an averaged vitamin A intake index was calculated. Stomach cancer cases showed a significantly higher proportion with lowered total vitamin A intake levels (odds ratio = 1.71) which remained constant across sex and socioeconomic status groupings. These results demonstrated a consistency with previous related studies vis-à-vis the strength and specificity of the putative association, a moderate (but statistically nonsignificant) dose-response curve, proper temporal association, and biologic plausibility.

Amateur radio operators and exposure to polychlorinated biphenyls.

In September, 1982, the Special Studies Branch, Chronic Diseases Division, Center for Environmental Health, Centers for Disease Control, was alerted to the possibility that oils in certain oil-filled devices used by amateur radio operators throughout the country were contaminated with polychlorinated biphenyls (PCBs). To evaluate the possible exposures and concomitant health risks, we conducted an exposure assessment study in two phases: an evaluation of the prevalence of environmental contaminations and an assessment of human exposure. Of 77 oil samples collected, only 2 were contaminated above a 50-ppm level; analyses of blood specimens collected from these two owner-operators showed serum PCB-levels which were well within a "normal" or expected background range. Although, on the basis of these limited data, PCBs from contaminated oils do not appear to be a hazard to amateur radio operators, we recommend that PCB-contaminated oils should not be used because of the continuing potential for exposure from either inhalation or direct contamination.

Assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure using a modified D-glucaric acid assay.

An enzyme-inhibition assay was evaluated and modified to quantify D-glucaric acid in a population exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The modified assay combined improvements described separately in previous reports, including pH adjustment by standard addition of buffers rather than by titration, an optimum pH of 2.3 for converting D-glucaric acid to 1,4-glucarolactone, and the use of the relation reciprocal of absorbance versus concentration for calculating unknowns. Reference limits for adult males were 0.06-5.90 mmol D-glucaric acid/mol creatinine and for adult females 0.87-6.23 mmol D-glucaric acid/mol creatinine. Children under the age of 15 yr had a reference range of 0-8.34 mmol D-glucaric acid/mol creatinine. Persons on anticonvulsant therapy excreted from 3 to 10 times the upper reference limits of D-glucaric acid. Urinary concentrations of D-glucaric acid in persons identified as being at high risk for exposure to 2,3,7,8-TCDD in Times Beach, Mo., were not significantly different from concentrations in those identified as being at low risk for such exposure.