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April 18, 1986, Vol 255, No. 15 >
ARTICLE | April 18, 1986

Health Effects of Long-term Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin FREE

Richard E. Hoffman, MD; Paul A. Stehr-Green, DrPH; Karen B. Webb, MD; R. Gregory Evans, PhD; Alan P. Knutsen, MD; Wayne F. Schramm, MA; Jeff L. Staake, MPA; Bruce B. Gibson; Karen K. Steinberg, PhD
[+] Author Affiliations

Use of trade names is for identification only and does not constitute endorsement by the Public Health Service or by the US Department of Health and Human Services.

Reprint requests to Division of Environmental Hazards and Health Effects, Center for Environmental Health, Centers for Disease Control, Atlanta, GA 30333 (Dr Hoffman).


JAMA. 1986;255(15):2031-2038. doi:10.1001/jama.1986.03370150073031
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References

In 1971, sludge wastes contaminated with 2,3,7,8-tetrachlorodibenzop-dioxin were mixed with waste oil and sprayed on a dirt road at the Quail Run Mobile Home Park in Gray Summit, Mo. We performed a comprehensive examination of 154 exposed and 155 unexposed persons in the area. There were no consistent differences between the two groups on medical history, physical examination, serum and urinary chemistry studies, and neurologic tests. Results of liver function tests suggested possible subclinical effects. The exposed group had an increased frequency of anergy (11.8% vs 1.1%) and relative anergy (35.3% vs 11.8%). The exposed group also had non-statistically significant increased frequencies of abnormal T-cell subset test results (10.4% vs 6.8%), a T4/T8 ratio of less than 1.0 (8.1% vs 6.4%), and an abnormality in the functional T-cell test results (12.6% vs 8.5%). These findings suggest that long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin is associated with depressed cell-mediated immunity, although the effects have not resulted in an excess of clinical illness in the exposed group. Further studies are indicated to elucidate the pathophysiology and clinical significance of these immunologic findings.

(JAMA 1986;255:2031-2038)

REFERENCES

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 +
 Health-risk estimates for 2,3,7,8-tetrachlorodibenzodioxin in soil . MMWR 1984;;33:25-27.
3 +
US Environmental Protection Agency:  National Pollutant Discharge Elimination System permit application testing requirements, appendix D . Federal Register 1983;;48( (April 1) ):14176-14177.
4 +
Arezzo JC, Schaumburg HH, Petersen CA:  Rapid screening for peripheral neuropathy: A field study with the optacon . Neurology 1983;; 33:626-629.
5 +
The Sorbinol Neuropathy Study Group:  Tactile (TT) and thermal threshold (ThT) testing in diabetic neuropathy , abstracted. Diabetes 1985;;34( (suppl 1) ):12A.
6 +
Johnson BL:  Report of international meeting on neurotoxicology . Neurotoxicology 1983;; 4:177-178.
7 +
Reitan RM:  Investigation of validity of Halstead's measures of biological intelligence . Arch Neurol Psychiatry 1955;;73:28-35.
8 +
Derogatis LR:  Self-report measures of stress , in Goldberger L, Breznitz S (eds): Handbook of Stress . New York, The Free Press, 1982;, pp 270-294.
9 +
Hollingshead A: Two Factor Index of Social Position . New Haven, Conn, Yale University Press, 1957;.
10 +
Hoffman RA, Kung PC, Hansen WP, et al:  Simple and rapid measurement of human T lymphocytes and their subclasses in peripheral blood . Proc Natl Acad Sci USA 1981;;77:4914-4917.
11 +
Schiff RI, Buckley AH, Gilbertson RB, et al:  Membrane receptors and in vitro responsiveness of lymphocytes in human immunodeficiency . J Immunol 1974;;112:376-386.
12 +
Namiuchi S, Kumagi S, Imura H, et al:  Quinacrine inhibits the primary but not the secondary proliferative response of human cytotoxic T cells to allogeneic non-T cell antigens . J Immunol 1984;;132:1456-1461.
13 +
Steinberg KK, MacNeil ML, Karon JM, et al:  Assessment of 2,3,7,8-tetrachlorodibenzodioxin exposure using a modified D-glucaric acid assay . J Toxicol Environ Health 1985;;16:743-752.
14 +
Hill RH, Bailey SL, Needham LL:  Development and utilization of a procedure for measuring urinary porphyrin by high-performance liquid chromatography . Chromatography 1982;; 232:251-260.
15 +
Paigen K, Peterson J:  Coordinacy of lysozomal enzyme excretion in human urine . J Clin Invest 1978;;61:751-762.
16 +
Jung K, Scholz D:  An optimized assay of alanine aminopeptidase activity in urine . Clin Chem 1980;;26:1251-1254.
17 +
Arkesteijn CL:  A kinetic method for serum 5′-nucleotidase using stabilized glutamate dehydrogenase . J Clin Chem Clin Biochem 1976;; 14:155-158.
18 +
Habig WH, Pabst MJ, Jakoby WB:  Glutathione-s-transferases: The first enzymatic step in mercapturic acid formation . J Biol Chem 1974;;249:7130-7139.
19 +
Kniker WT, Anderson CT, McBryde JL, et al:  Multitest CMI for standardized measurement of delayed cutaneous hypersensitivity and cell-mediated immunity: Normal values and proposed scoring system for healthy adults in the U.S.A. Ann Allerg 1984;;52:75-82.
20 +
Corriel RN, Kniker WT, McBryde JL, et al:  Cell-mediated immunity in school children assessed by multitest skin testing . AJDC 1985;; 139:141-146.
21 +
Knutsen AP:  Immunologic effects of TCDD exposure in humans . Bull Environ Contam Toxicol 1984;;33:673-681.
22 +
Reuben JM, Hersh EM:  Delayed hypersensitivity responses of cancer patients to recall antigens using a new 'Multitest' applicator . Ann Allerg 1984;;53:390-394.
23 +
Hersh EM, Reuben JM:  Delayed hypersensitivity testing in symptom-free homosexuals, AIDS, and ARC patients , in Fauci AS (ed): Focus on AIDS: A Clinical Appraisal . New York, Park Row Publishers, 1984;, pp 17-21.
24 +
Carle G, Duncan JL, Champagne C, et al:  A new device for delayed hypersensitivity skin testing . J Am Coll Nutr 1985;;4:515-520.
25 +
Christou NV:  Anergy testing in surgical patients . Infect Surg , (October) 1983;, pp 692-700.
26 +
Vos JG, Faith RE, Luster MI:  Immune alterations , in Kimbrough RD (ed): Halogenated Biphenyls, Terphenyls, Naphthalenes, DibenzoDioxins and Related Products . Amsterdam, Elsevier Science Publishers, 1980;, pp 248-254.
27 +
Vos JG, Moore JA, Zinkl JG:  Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57B1/6 mice . Toxicol Appl Pharmacol 1974;; 29:229-241.
28 +
Clark DA, Gauldie J, Szewczuk MR, et al:  Enhanced suppressor cell activity as a mechanism of immunosuppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (41275) . Proc Soc Exp Biol Med 1981;;168:290-299.
29 +
Faith RE, Luster MI:  Investigations on the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on parameters of various immune functions . Ann NY Acad Sci 1979;;320:564-571.
30 +
Faith RE, Luster MI, Moore JA:  Chemical separation of helper cell function and delayed hypersensitivity responses . Cell Immunol 1978;; 40:275-284.
31 +
Reite M, Harbeck R, Hoffman A:  Altered cellular immune response following peer separation . Life Sci 1981;;29:1133-1136.
32 +
Barthrop RW, Luckhurst E, Lazarus L, et al:  Depressed lymphocyte function after bereavement . Lancet 1977;;1:834-836.
33 +
Schleifer SJ, Keller SE, Camerino M, et al:  Suppression of lymphocyte stimulation following bereavement . JAMA 1983;;250:374-377.
34 +
Esposito MP, Tiernan TO, Dryden FE: Dioxins . Cincinnati, US Environmental Protection Agency, 1980;, pp 223-225.
35 +
 Missouri Division of Health, Centers for Disease Control, St Joseph Hospital of Kirkwood, St Louis University School of Medicine : Missouri Dioxin Health Studies Progress Report . Jefferson City, Missouri Department of Health, 1983;, p 67.
36 +
Esposito MP, Tiernan TO, Dryden FE: Dioxins . Cincinnati, US Environmental Protection Agency, 1980;, pp 208-210.
37 +
Esposito MP, Tiernan TO, Dryden FE: Dixoins . Cincinnati, US Environmental Protection Agency, 1980;, pp 187-195.
38 +
Martin PJ, Martin JB, Goldberg DM:  Gamma glutamyl transpeptidase, triglycerides, and enzyme induction . Br Med J 1975;;1:17-18.
39 +
Tutor JC, Fernandez MP, Paz JM, et al:  Serum activity of the beta glucuronidase in patients treated with phenobarbital and diphenylhydantoin . Arch Pharmacol Toxicol 1982;; 8:37-44.
40 +
Hirayama C, Okmura M, Hagia J, et al:  Hypobilirubinemia in patients with polychlorinated biphenyl poisoning . Clin Chem Acta 1974;; 55:97-100.
41 +
Hunter J, Maxwell JD, Carrella M, et al:  Urinary D-glucaric acid excretion as a test for hepatic enzyme induction in man . Lancet 1971;; 1:572-575.
42 +
Ideo G, Bellati G, Bellobuono A, et al:  Increased urinary D-glucaric acid tetrachlorodibenzodioxin (TCDD) . Clin Chim Acta 1982;; 120:273-283.
43 +
Crow KD:  Chloracne . Semin Dermatol 1982;;1:305-314.
44 +
Council on Scientific Affairs:  Health effects of agent orange and dioxin contaminants . JAMA 1982;;248:1896.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

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 +
 Health-risk estimates for 2,3,7,8-tetrachlorodibenzodioxin in soil . MMWR 1984;;33:25-27.
3 +
US Environmental Protection Agency:  National Pollutant Discharge Elimination System permit application testing requirements, appendix D . Federal Register 1983;;48( (April 1) ):14176-14177.
4 +
Arezzo JC, Schaumburg HH, Petersen CA:  Rapid screening for peripheral neuropathy: A field study with the optacon . Neurology 1983;; 33:626-629.
5 +
The Sorbinol Neuropathy Study Group:  Tactile (TT) and thermal threshold (ThT) testing in diabetic neuropathy , abstracted. Diabetes 1985;;34( (suppl 1) ):12A.
6 +
Johnson BL:  Report of international meeting on neurotoxicology . Neurotoxicology 1983;; 4:177-178.
7 +
Reitan RM:  Investigation of validity of Halstead's measures of biological intelligence . Arch Neurol Psychiatry 1955;;73:28-35.
8 +
Derogatis LR:  Self-report measures of stress , in Goldberger L, Breznitz S (eds): Handbook of Stress . New York, The Free Press, 1982;, pp 270-294.
9 +
Hollingshead A: Two Factor Index of Social Position . New Haven, Conn, Yale University Press, 1957;.
10 +
Hoffman RA, Kung PC, Hansen WP, et al:  Simple and rapid measurement of human T lymphocytes and their subclasses in peripheral blood . Proc Natl Acad Sci USA 1981;;77:4914-4917.
11 +
Schiff RI, Buckley AH, Gilbertson RB, et al:  Membrane receptors and in vitro responsiveness of lymphocytes in human immunodeficiency . J Immunol 1974;;112:376-386.
12 +
Namiuchi S, Kumagi S, Imura H, et al:  Quinacrine inhibits the primary but not the secondary proliferative response of human cytotoxic T cells to allogeneic non-T cell antigens . J Immunol 1984;;132:1456-1461.
13 +
Steinberg KK, MacNeil ML, Karon JM, et al:  Assessment of 2,3,7,8-tetrachlorodibenzodioxin exposure using a modified D-glucaric acid assay . J Toxicol Environ Health 1985;;16:743-752.
14 +
Hill RH, Bailey SL, Needham LL:  Development and utilization of a procedure for measuring urinary porphyrin by high-performance liquid chromatography . Chromatography 1982;; 232:251-260.
15 +
Paigen K, Peterson J:  Coordinacy of lysozomal enzyme excretion in human urine . J Clin Invest 1978;;61:751-762.
16 +
Jung K, Scholz D:  An optimized assay of alanine aminopeptidase activity in urine . Clin Chem 1980;;26:1251-1254.
17 +
Arkesteijn CL:  A kinetic method for serum 5′-nucleotidase using stabilized glutamate dehydrogenase . J Clin Chem Clin Biochem 1976;; 14:155-158.
18 +
Habig WH, Pabst MJ, Jakoby WB:  Glutathione-s-transferases: The first enzymatic step in mercapturic acid formation . J Biol Chem 1974;;249:7130-7139.
19 +
Kniker WT, Anderson CT, McBryde JL, et al:  Multitest CMI for standardized measurement of delayed cutaneous hypersensitivity and cell-mediated immunity: Normal values and proposed scoring system for healthy adults in the U.S.A. Ann Allerg 1984;;52:75-82.
20 +
Corriel RN, Kniker WT, McBryde JL, et al:  Cell-mediated immunity in school children assessed by multitest skin testing . AJDC 1985;; 139:141-146.
21 +
Knutsen AP:  Immunologic effects of TCDD exposure in humans . Bull Environ Contam Toxicol 1984;;33:673-681.
22 +
Reuben JM, Hersh EM:  Delayed hypersensitivity responses of cancer patients to recall antigens using a new 'Multitest' applicator . Ann Allerg 1984;;53:390-394.
23 +
Hersh EM, Reuben JM:  Delayed hypersensitivity testing in symptom-free homosexuals, AIDS, and ARC patients , in Fauci AS (ed): Focus on AIDS: A Clinical Appraisal . New York, Park Row Publishers, 1984;, pp 17-21.
24 +
Carle G, Duncan JL, Champagne C, et al:  A new device for delayed hypersensitivity skin testing . J Am Coll Nutr 1985;;4:515-520.
25 +
Christou NV:  Anergy testing in surgical patients . Infect Surg , (October) 1983;, pp 692-700.
26 +
Vos JG, Faith RE, Luster MI:  Immune alterations , in Kimbrough RD (ed): Halogenated Biphenyls, Terphenyls, Naphthalenes, DibenzoDioxins and Related Products . Amsterdam, Elsevier Science Publishers, 1980;, pp 248-254.
27 +
Vos JG, Moore JA, Zinkl JG:  Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57B1/6 mice . Toxicol Appl Pharmacol 1974;; 29:229-241.
28 +
Clark DA, Gauldie J, Szewczuk MR, et al:  Enhanced suppressor cell activity as a mechanism of immunosuppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (41275) . Proc Soc Exp Biol Med 1981;;168:290-299.
29 +
Faith RE, Luster MI:  Investigations on the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on parameters of various immune functions . Ann NY Acad Sci 1979;;320:564-571.
30 +
Faith RE, Luster MI, Moore JA:  Chemical separation of helper cell function and delayed hypersensitivity responses . Cell Immunol 1978;; 40:275-284.
31 +
Reite M, Harbeck R, Hoffman A:  Altered cellular immune response following peer separation . Life Sci 1981;;29:1133-1136.
32 +
Barthrop RW, Luckhurst E, Lazarus L, et al:  Depressed lymphocyte function after bereavement . Lancet 1977;;1:834-836.
33 +
Schleifer SJ, Keller SE, Camerino M, et al:  Suppression of lymphocyte stimulation following bereavement . JAMA 1983;;250:374-377.
34 +
Esposito MP, Tiernan TO, Dryden FE: Dioxins . Cincinnati, US Environmental Protection Agency, 1980;, pp 223-225.
35 +
 Missouri Division of Health, Centers for Disease Control, St Joseph Hospital of Kirkwood, St Louis University School of Medicine : Missouri Dioxin Health Studies Progress Report . Jefferson City, Missouri Department of Health, 1983;, p 67.
36 +
Esposito MP, Tiernan TO, Dryden FE: Dioxins . Cincinnati, US Environmental Protection Agency, 1980;, pp 208-210.
37 +
Esposito MP, Tiernan TO, Dryden FE: Dixoins . Cincinnati, US Environmental Protection Agency, 1980;, pp 187-195.
38 +
Martin PJ, Martin JB, Goldberg DM:  Gamma glutamyl transpeptidase, triglycerides, and enzyme induction . Br Med J 1975;;1:17-18.
39 +
Tutor JC, Fernandez MP, Paz JM, et al:  Serum activity of the beta glucuronidase in patients treated with phenobarbital and diphenylhydantoin . Arch Pharmacol Toxicol 1982;; 8:37-44.
40 +
Hirayama C, Okmura M, Hagia J, et al:  Hypobilirubinemia in patients with polychlorinated biphenyl poisoning . Clin Chem Acta 1974;; 55:97-100.
41 +
Hunter J, Maxwell JD, Carrella M, et al:  Urinary D-glucaric acid excretion as a test for hepatic enzyme induction in man . Lancet 1971;; 1:572-575.
42 +
Ideo G, Bellati G, Bellobuono A, et al:  Increased urinary D-glucaric acid tetrachlorodibenzodioxin (TCDD) . Clin Chim Acta 1982;; 120:273-283.
43 +
Crow KD:  Chloracne . Semin Dermatol 1982;;1:305-314.
44 +
Council on Scientific Affairs:  Health effects of agent orange and dioxin contaminants . JAMA 1982;;248:1896.

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