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2,3,7,8-Tetrachlorodibenzo-p-Dioxin Levels In Adipose Tissue Of Persons With No Known Exposure And In Exposed Persons

    John S. Andrews, Jr. , Woodrow A. Garrett, Jr., Donald G. Patterson, Jr.
    Larry L. Needham, Daryl W. Roberts, John R. Bagby, John E. Anderson
    Richard E. Hoffman, and Wayne Schramm

    1Center for Environmental Health and Injury Control, Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia, 30333, Tel. 404–488–4682.

    2Missouri Department of Health, Jefferson City, Missouri, 65102–0570, Tel. 314–751–6111.

    Abstract Adipose tissue tetrachlorodibenzo-p-dioxin (TCDD) levels were determined for 128 persons with no known exposure and for 51 exposed persons. For persons with no known exposure, adipose TCDD levels ranged from nondetectable to 20.2 ppt with 95% of the levels at 16.6 ppt or less. For the 51 exposed persons, adipose tissue TCDD levels ranged from 3.7–750 ppt.

    INTRODUCTION

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was produced as an unwanted contaminant during the production of trichlorophenol (TCP) at a chemical facility in Missouri between 1968 and 1971. TCP is an intermediate compound that is used in the production of both 2,4,5-trichlorophenoxyacetic acid and hexachlorophene (1). In 1971, approximately 29 kg of TCDD-contaminated sludge wastes were mixed with waste oils and sprayed for dust control on horse arenas, parking lots, and unpaved roads in the eastern part of Missouri (2). In most of these areas, TCDD exposure continued until 1982 or later, depending on when the site was identified and testing was completed. As of July 1988, more than 250 sites in Missouri had been investigated or were awaiting investigation, and 5,000 persons were estimated to have been exposed. This study was designed primarily as a feasibility study to determine if elevated adipose tissue TCDD levels could be demonstrated in a group of persons who were thought to have been exposed to TCDD as compared with a group of persons with no known TCDD exposure.

    METHODS

    From questionnaire responses alone, all potential participants were classified by study personnel as having no known exposure or as being exposed. The questionnaire included questions on age, sex, race, and current postal code of residence in three areas of Missouri (Kansas City, St. Louis, or Springfield); potential sources of TCDD exposure; and a variety of other variables.

    For this study persons were considered to have been exposed to TCDD if they lived, worked, or had contact for 2 years or more with soil contaminated with TCDD at levels of 20–100 ppb or for 6 months or more with soil contaminated with TCDD at levels greater than 100 ppb. Potentially exposed participants were recruited from areas where TCDD-contamination was known to have occurred.

    Persons were considered to have no known exposure if they did not meet any of the exposure criteria listed above and if the soil in areas where they lived and carried out their main activities was not known to have TCDD levels greater than 1 ppb. All of the participants with no known exposure lived in postal code areas thought to be without TCDD contamination, however, for many of them, soil from the areas where they carried out their main activities was not tested. Persons with no known exposure were recruited from the group of persons who were undergoing elective abdominal surgery in one of three hospitals in Kansas City, St. Louis, or Springfield. Unexposed participants were enrolled according to a sampling matrix of various age, sex, race, and residential area strata from the three areas listed above.

    For all participants, 10–20 g of anterior wall adipose tissue were collected by a surgical procedure according to a standard protocol. Adipose tissue specimens were analyzed by high-resolution gas chromatography/high-resolution mass spectrometry with a detection limit of 1 ppt on a whole-weight basis (3–5). A 1.6-ppt or an 8.4-ppt quality control pool sample was used in every run. Statistical data were analyzed by using stepwise regression techniques (Statistical Analysis System, Version 5 program package).

    After adipose tissue TCDD concentrations were determined, exposed participants were classified into four exposure groups: 1) persons exposed at work in the production of TCP; 2) persons exposed at work other than in the production of TCP, such as hauling waste from the TCP production facility, working in the laboratory or in maintenance at the TCP production facility, or working at one of several truck terminals where TCDD-contaminated oil had been sprayed for dust control; 3) persons who had ridden or cared for horses at one of several horse arenas that had been sprayed with TCDD-contaminated oil for dust control; and 4) persons exposed in residential areas where residential soil or streets had been sprayed with TCDD-contaminated oil for dust control.

    RESULTS

    Study participants ranged in age from 18 to 78 years. One hundred sixty-nine (94%) of the 179 participants were white. Data regarding the age, sex, and area of residence for the 128 participants with no known exposure and for the 51 exposed persons are shown in Table 1. The age distribution of participants with no known exposure does not approximate the age distribution of the estimated 1986 United States population (6). Persons 0–17 years of age were not included in the study, but they comprise 26.3% of the estimated 1986 United States population 18 years of age and above is as follows: 18–29 years = 28.0%, 30–39 years = 22.3%, 40–49 years = 14.8%, 50–59 years, 12.5%, 60 years and above = 22.5%.

    TABLE 1
     
    AGE, SEX, AND AREA OF RESIDENCE FOR ALL 179 PARTICIPANTS
    IN 2,3,7,8-TCDD EXPOSURE STUDY
    MISSOURI, 1986
     

    NO KNOWN EXPOSURE

    		  

    EXPOSED
     

    KANS CTY

    ST LOUIS

    SPRINGFD

    TOTAL

    		  

    ST LOUIS

    SPRINGFD

    TOTAL
    AGE (yrs)

    M

    F

    M

    F

    M

    F

    (%)

    		  

    M

    F

    M

    F

    (%)
    18–29

    0

    3

    7

    3

    0

    1

    14      (10.9)

    		  

    3

    5

    0

    0

     8    (15.7)
    30–39

    2

    7

    5

    6

    3

    7

    30      (23.4)

    		  

    5

    5

    4

    0

    14    (27.4)
    40–49

    1

    6

    4

    5

    1

    8

    25      (19.5)

    		  

    3

    2

    3

    1

     9    (17.6)
    50–59

    2

    6

    3

    3

    2

    6

    22      (17.2)

    		  

    5

    2

    5

    0

    12    (23.5)
    60+

    6

    4

    7

    6

    8

    6

    37      (28.9)

    		  

    4

    1

    3

    0

     8   (15.7)
     

    11

    26

    26

    23

    14

    28

    128    (100.0)  

    		  

    20

    15

    15

    1

    51  (100.0)

    M=MALE     F=FEMALE

    KANS CTY=Kansas City       ST LOUIS=St Louis      SPRINGFD=Springfield

    The age distributions of the persons with no known exposure and the exposed persons were different. Therefore, the adipose tissue TCDD ranges, means, and standard deviations were determined separately for males and females in five separate age groups. In the regression analyses, age was entered as an independent variable in the models.

    For persons with no known exposure, adipose tissue TCDD concentrations ranged from nondetectable to 20.2 ppt (Figure 1). Ninety-five percent of the values were 16.6 ppt or lower with a mean of 7.0 ppt, a standard deviation of 4.0 ppt, and a median of 6.1 ppt. Table 2 shows the adipose tissue TCDD levels by age and sex for the participants with no known exposure. Overall, adipose tissue TCDD levels increased by approximately 20% per decade for both men and women. This is consistent with the findings of others (7–8).

    There was no relationship between adipose tissue TCDD level and educational level, the presence or absence of a lawn service, or the presence or absence of a pesticide service. When the natural logarithm of the adipose tissue TCDD level was used as the outcome variable and all of the variables in the questionnaire were placed in the model, only age, years at current residence, residence in the St. Louis area, and female sex were

    ADIPOSE TISSUE TCDD LEVELS
    IN UNEXPOSED PERSONS
    MISSOURI 1986
    FIGURE 1

    ADIPOSE TISSUE TCDD LEVELS
    IN EXPOSED PERSONS
    MISSOURI 1986
    FIGURE 2

    TABLE 2

    ADIPOSE TISSUE TCDD LEVELS IN PPT BY SEX AND AGE IN YEARS
    FOR THE 128 PARTICIPANTS WITH NO KNOWN EXPOSURE IN 2,3,7,8-TCDD EXPOSURE STUDY
    MISSOURI, 1986

     

    MALES

    AGE

    #

    RANGE

    MEAN

    S.D.

    MEDIAN
     

    18–29

    7

    1.4  –  6.8

    4.5

    1.9

    4.7
     

    30–39

    10

    2.0  –10.4

    5.2

    2.7

    4.5
     

    40–49

    6

    2.8  –  7.3

    4.9

    1.6

    4.7
     

    50–59

    7

    4.7  –11.7

    6.8

    2.4

    5.9
     

    60  +  

    21

    N.D. –20.0 

    8.9

    5.2

    6.9
     

    TOTAL

    51

    N.D. –20.0 

    6.8

    4.1

    5.6
    FEMALES

    AGE

    #

    RANGE

    MEAN

    S.D.

    MEDIAN
     

    18–29

    7

    1.4 –  8.2

    3.4

    2.4

    2.4
     

    30–39

    20

    2.4 –20.2

    6.3

    4.0

    5.3
     

    40–49

    19

    2.9 –  8.3

    5.7

    1.6

    5.3
     

    50–59

    15

    4.0 –17.8

    8.6

    3.8

    7.7
     

    60  +  

    16

    5.4 –17.8

    10.3

    4.2

    9.6
     

    TOTAL

    77

    1.4 –20.2

    7.2

    4.0

    6.4

    N.D.=nondetectable

    significantly associated with the adipose tissue TCDD level (Table 3). Age and years at current residence were independent predictors of the adipose tissue TCDD levels. The finding that age is a predictor of adipose tissue TCDD level is consistent with other TABLE 3

    REGRESSION ANALYSIS FOR THE 128 PARTICIPANTS WITH NO KNOWN EXPOSURE
    IN 2,3,7,8-TCDD EXPOSURE STUDY
    MISSOURI, 1986
    (USING THE NATURAL LOGARITHM OF ADIPOSE TISSUE TCDD LEVELS)

    TERM

    REG COEF

    S.E.

    P
    Intercept

    0.808

    0.145

    <0.001
    Age in years

    0.018

    0.003

    <0.001
    Yrs residence

    0.001

    0.000

    0.019
    Res in St. Louis

    0.222

    0.090

    0.015
    Female

    0.218

    0.089

    0.016

    R-SQUARE =.36

    studies of lipid soluble compounds. However, we have no explanation for the finding that years at current residence was also a predictor.

    All exposed participants had exposure in only one exposure group. Their adipose tissue TCDD levels ranged from 3.7–750 ppt (Table 4 and Figure 2). The range, mean, and median adipose tissue TCDD concentrations are shown in Table 4. There were significant differences in adipose tissue TCDD levels for the persons with no known exposure versus all 51 exposed persons, and for three of the four exposure categories (TCP production, horse arena exposure, and residential exposure [p < 0.001, t-test]). Only six (12%) of the

    TABLE 4

    ADIPOSE TISSUE TCDD LEVELS IN PPT
    IN 51 EXPOSED STUDY PARTICIPANTS IN 2,3,7,8 TCDD EXPOSURE STUDY
    MISSOURI, 1986

    EXPOSURE STATUS

    #

    RANGE

    MEAN

    S.D.

    MEDIAN
    TCP PRODUCTION

    9

    41.9–750

    245

    287

    122
    HORSE ARENA

    16  

    5.0–577

    145

    202

     24.1
    RESIDENTIAL

    16  

     26.8

     18.9

     19.5
    WASTE HAULING

    10  

     12.4

    8.3

    9.0

    exposed participants had adipose TCDD levels less than the 6.1 ppt, the median adipose tissue TCDD levels measured in participants with no known exposure.

    Participants from each of the four exposed groups had adipose tissue TCDD levels that exceeded 20.2 ppt, the highest adipose tissue TCDD level measured in persons with no known exposure (Table 4 and Figure 2). Persons who were exposed at work in TCP production and in riding or caring for horses had the highest mean and median adipose tissue TCDD levels. All of the adipose tissue TCDD levels greater than 100 ppt were in persons in these two exposure groups.

    Eighteen or 35% of the persons thought to have been exposed to TCDD on the basis of questionnaire data had adipose tissue TCDD levels of 16.6 ppt or less. Twenty-two (43%) of the 51 exposed participants had adipose tissue TCDD levels of 20.2 ppt or less. Thirty-six (71%) of the exposed participants had adipose tissue TCDD levels of 50 ppt or less.

    Fifteen of the 16 persons exposed to TCDD in residential areas were residents of the areas; one person worked in one of the residential areas. For the 15 residents, there was no relationship of adipose tissue TCDD level with activities such as eating homegrown vegetables, gardening, mowing the lawn, participating in field sports in the yard, bicycling, walking, or other activities involving exposure to soil.

    If it is assumed that the half-life of TCDD in the human body is 7 years (9) and that the last date of exposure for the persons in TCP production was 1971, it is likely that at the time of exposure two of the study participants had adipose tissue TCDD levels near 3,000 ppt. All of the exposed participants have been offered medical examinations. The results of these examinations are being analyzed.

    CONCLUSION

    A cross-sectional study of 128 persons with no known exposure to TCDD and 51 persons who were thought to have been exposed was carried out. All but one person had detectable adipose tissue TCDD. Questionnaire information made it possible to identify categories of exposed persons on the basis of activities. In persons with no known exposure, adipose tissue TCDD levels ranged from nondetectable to 20.2 ppt on a whole-weight basis with 95% of the levels 16.6 ppt or less. Thirty-five percent of the persons thought to have been exposed to TCDD from questionnaire responses had adipose tissue TCDD levels at or below 95% of the adipose tissue TCDD levels of the persons with no known exposure (16.6 ppt or lower). An objective measure of adipose tissue TCDD makes it possible to minimize misclassification when studying the association of TCDD exposure and health effects.

    Notably, this study includes persons in each of the 10-year age groups from 19–69 years, of both sexes, from three different areas of Missouri. Because of the small number of nonwhite participants, the effect of race on adipose tissue TCDD levels could not be evaluated. From this study it is possible to predict that 95% of adipose tissue TCDD levels for persons with no known exposure would be 16.6 ppt or lower. The factors used in selecting this population, however, make it impossible to say that this value is truly a normal range. It is not possible to know how representative the participants are of other parts of Missouri or the United States. As was reported in the interim report of this study (9), the adipose tissue TCDD levels observed in persons with no known TCDD exposure are similar to the levels seen in autopsy specimen studies reported by several other investigators (7–8, 10–13). The current study includes adipose tissue TCDD results of 179 persons, the largest number reported to date.

    The Centers for Disease Control has recently developed a technique for measuring TCDD in human serum on a whole-weight basis in the parts per quadrillion range (14). The results from serum analyses correlate very well with the adipose tissue TCDD results, making a surgical procedure unnecessary (15). These correlations also agree with other reports (16).

    ACKNOWLEDGMENTS

    This study was conducted under a cooperative agreement between the Missouri Department of Health and the Centers for Disease Control. It was supported by funds from the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) trust fund by interagency agreement with the Agency for Toxic Substances and Disease Registry (ATSDR), U.S. Public Health Service. The use of trade names is for identification only and does not constitute endorsement by the U.S. Public Health Service or the Missouri Department of Health. The following persons contributed to the study: Drs. Henry Falk, Eric J. Sampson, Vernon N. Houk, Louis R. Alexander, Ralph C. O'Connor, Paul A. Stehr-Green, John Liddle, Paul Koontz, Donald Kaminski, Francis X. Paletta, Sr., Francis X. Paletta, Jr., and R. Gregory Evans. Chester R. Lapeza, William T. Belser, Vincent Maggio, Vaughn Green, Sandy Isaacs, Jim Gill, S. Jay Smith, Brenda Lewis, Debbi Kotlovker, Cindy Kempker, Tina Luebbering, Sonjia Grotewiel, Miriam JoAnn Wollard, Rebecca Snow, Beverly Heinzelman, Jeff Staake, David Forney, Florence Neider, Mary Frey, and Bruce B. Gibson also contributed to the study.

    REFERENCES

      United States Environmental Protection Agency: Dioxins. 1980, pp. 1–351. EPA-600/2–80–197. Available from the National Technical Information Service, Springfield, VA 22161.

    1. Stehr PA, Forney D, Stein G, et al: The public health response to 2,3,7,8-TCDD environmental contamination in Missouri. Public Health Rep 1985;100:289–293.

    2. Albro PW, Crummett WB, Dupuy AE Jr, et al: Methods for the quantitative determination of multiple, specific polychlorinated dibenzo-p-dioxin and dibenzofuran isomers in human adipose tissue in the parts-per-trillion range: An interlaboratory study. Anal Chem 1985;57:2717–2725.

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    8. Patterson DG Jr, Hoffman RE, Needham LL, et al: 2,3,7,8-Tetrachlorodibenzo-p-dioxin levels in adipose tissue of exposed and control persons in Missouri: An interim report. JAMA 1986;256:2683–2686.

    9. Ryan JJ, Williams DJ: Abstracts of the 186th American Chemical Society Meeting, Environmental Chemistry Section, abstract 55. Washington, DC, American Chemical Society, 1983, p 157.

    10. Kutz FW: Chemical Exposure Monitoring in the Environmental Protection Agency (EPA) Office of Pesticides and Toxic Substances, prepared statement to the Veterans Administration Advisory Committee on Health Effects of Herbicides, Washington, DC, 1981.

    11. Graham M, Hileman FD, Kirk D, et al: Background human exposure to 2,3,7,8-TCDD. Read before the Fourth International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa, Oct 16–18, 1984.

    12. Gross ML, Lay JO, Lyon PA, et al: 2,3,7,8-Tetrachlorodibenzo-p-dioxin levels in adipose tissue of Vietnam veterans. Environ Res 1984;33:261–268.

    13. Patterson DG Jr, Hampton L, Lapeza CR Jr, et al: High-resolution gas chromatographic/high-resolution mass spectrometric analysis of human serum on a whole-weight and lipid basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Anal Chem 1987;59:2000–2005.

    14. Patterson DG Jr, Needham LL, Pirkle JL, et al: Correlation between human serum and adipose concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin in fifty persons from Missouri. Arch Environ Contam Toxicol 1988;17:139–143.

    15. Kahn PC, Gochfeld M, Nygren M, et al: Dioxins and dibenzofurans in blood and adipose tissue of agent orange-exposed Vietnam veterans and matched controls. JAMA 1988;259:1661–1667.

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