Immunological markers among workers exposed to 2,3,7,8- tetrachlorodibenzo-p-dioxin

OBJECTIVES: To examine the association of immune cell number and function with occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). METHODS: A cross sectional medical survey. The exposed participants were employed at two chemical plants between 1951 and 1972 in the manufacture of 2,4,5- trichlorophenate and its derivatives. The reference group consisted of people with no occupational exposure to phenoxy herbicides who lived within the communities of the workers. Data from a total of 259 workers and 243 unexposed referents were included in the analysis of immune function. Laboratory tests for immune status included enumeration of circulating leukocyte and lymphocyte populations, proliferative responses of circulating lymphocytes to mitogens and antigens, and serum concentrations of the major immunoglobulins and complement factor C3. RESULTS: The workers had substantial exposure to substances contaminated with TCDD, as indicated by a lipid adjusted mean serum TCDD concentration of 229 ppt compared with a mean of 6 ppt in the unexposed referents. Workers were divided into categories based on their serum TCDD concentration. For all categories except the lowest, with values of serum TCDD comparable with the unexposed referents, there were increased odds of having lower counts of CD26 cells (activated T cells) (odds ratio (OR) 1.0, 95% confidence interval (95% CI) 0.5 to 1.8 for TCDD < 20 ppt; OR 1.6, 95% CI 0.8 to 3.2 for TCDD 20- 51 ppt; OR 2.7, 95% CI 1.4 to 5.1 for TCDD 52-125 ppt; OR 2.6, 95% CI 1.4 to 4.9 for TCDD 125-297 ppt; OR 2.4, 95% CI 1.3 to 4.6 for TCDD 298- 3389 ppt). A less consistent finding was decreased spontaneous proliferation of cultured lymphocytes. However, increases were found in proliferation of lymphocytes in response to concanavalin and pokeweed in workers in the high TCDD category. Age, cigarette smoking, and alcohol were significant predictors of several immunological outcomes. CONCLUSIONS: Associations between serum TCDD concentration and both a decrease in circulating CD26 cells and decreased spontaneous background proliferation were the major findings of this study. These results are unlikely to be of clinical importance but may reflect limited evidence for an association between immunological changes in workers and high serum concentrations of TCDD, or chance findings resulting from the evaluation of multiple immunological variables.

 

     

Food as a source of dioxin exposure in the residents of Bien Hoa City,Vietnam

Recently, elevated dioxin levels, over 5 parts per trillion (ppt) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), from Agent Orange was reported in 95% of 43 selected residents of Bien Hoa City, a city in southern Vietnam near a former air base used for Agent Orange-spraying missions. Agent Orange herbicide, contaminated with TCDD, was sprayed in Vietnam between 1962 and 1971 primarily for use as a defoliant. Typical blood TCCD levels are 2 ppt in Vietnamese, but levels are as high as 413 ppt in Bien Hoa City. Elevated TCDD was found in children born many years after Agent Orange spraying ended and in immigrants from non-Agent Orange-sprayed parts of Vietnam, which documented new exposures. Extremely elevated soil TCDD samples, over 1 million ppt, and elevated TCDD in sediment were found in some nearby areas such as Bien Hung Lake. The primary route of intake of almost all dioxins in humans is food. However, in our prior studies in Bien Hoa, food was unavailable for dioxin analysis so the route of intake was not confirmed. In the 1970s, while Agent Orange was still being sprayed, elevated human milk TCDD levels as high as 1850 were detected in milk from Vietnamese people living in Agent Orange-sprayed areas where consumption of fish was high. Furthermore, also in the 1970s, elevated TCDD levels (up to 810 ppt) were found in fish and shrimp from the same area as the milk donors. In the 1980s, we found elevated TCDD and also other organohalogen levels in human tissue, pork, fish, a turtle, and a snake in Southern Vietnam. For these reasons, we recently collected food from Bien Hoa and analyzed it for dioxins, polychlorinated biphenyls (PCBs), DDT and its metabolites, and other organochlorines. We found marked elevation of TCDD, the dioxin characteristic of Agent Orange, in some of the food products, including ducks with 276 ppt and 331 ppt wet weight, chickens from 0.031-15 ppt wet weight, fish from 0.063-65 ppt wet weight, and a toad with 56 ppt wet weight. Usual TCDD levels in food are less than 0.1 ppt. Total TEQ for ducks was from 286-343 ppt wet weight or 536 ppt and 550 ppt lipid; for chickens from 0.35-48 ppt wet weight or 0.95-74 ppt lipid, for fish from 0.19-66 ppt wet weight or 3.2 ppt and 15,349 ppt lipid, and the toad was 80 ppt wet weight and 11,765 ppt lipid. Interestingly, this study did not find elevated levels of TCDD in the pork and beef samples. Clearly, food, including duck, chicken, some fish, and a toad, appears responsible for elevated TCDD in residents of Bien Hoa City, even though the original Agent Orange contamination occurred 30-40 years before sampling. Elevated levels of PCBs and DDT and its metabolites were found in some food samples. Furthermore, measurable levels of hexachlorocyclohexanes (HCH) and hexachlorobenzene (HCB) were found in a wide range of measurable levels. All of the 11 dioxin-like PCBs measured and presented plus 6 dioxins in addition to TCDD and 10 dibenzofurans contributed to the total dioxin toxicity (TEQ). However, when elevated, TCDD frequently contributed most of the TEQ. Thirty-six congeners from 7 classes of chemicals were measured in each of the 16 specimens providing a total of 576 congener levels.     

Serum 2,3,7,8-Tetrachlorodibenzo-p-dioxin Levels and Their Association With Age,Body Mass Index,Smoking, Military Record-based Variables,and Estimated Exposure to Agent Orange in Korean Vietnam Veterans

Objectives

The aim of this study was to examine the levels of serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and evaluate their association with age, body mass index, smoking, military record-based variables, and estimated exposure to Agent Orange in Korean Vietnam veterans.

Methods

Serum levels of TCDD were analyzed in 102 Vietnam veterans. Information on age, body mass index, and smoking status were obtained from a self-reported questionnaire. The perceived exposure was assessed by a 6-item questionnaire. Two proximity-based exposures were constructed by division/brigade level and battalion/company level unit information using the Stellman exposure opportunity index model.

Results

The mean and median of serum TCDD levels was 1.2 parts per trillion (ppt) and 0.9 ppt, respectively. Only 2 Vietnam veterans had elevated levels of TCDD (>10 ppt). The levels of TCDD did not tend to increase with the likelihood of exposure to Agent Orange, as estimated from either proximity-based exposure or perceived self-reported exposure. The serum TCDD levels were not significantly different according to military unit, year of first deployment, duration of deployment, military rank, age, body mass index, and smoking status.

Conclusions

The average serum TCDD levels in the Korean Vietnam veterans were lower than those reported for other occupationally or environmentally exposed groups and US Vietnam veterans, and their use as an objective marker of Agent Orange exposure may have some limitations. The unit of deployment, duration of deployment, year of first deployment, military rank, perceived self-reported exposure, and proximity-based exposure to Agent Orange were not associated with TCDD levels in Korean Vietnam veterans. Age, body mass index and smoking also were not associated with TCDD levels.     

Dioxin and diabetes mellitus: an analysis of the combined NIOSH and Ranch Hand data

OBJECTIVES—To reanalyze in a similar manner the two principal studies of TCDD (tetrachlorodibenzo-p-dioxin) and diabetes in an attempt to reconcile disparate results.
METHODS—Data from 990 United States Air Force veterans (Ranch Hand) and 1275 referents were reanalyzed, and a NIOSH population of 267 chemical workers and 227 referents. The Ranch Hand veterans had lower concentrations of lipid adjusted serum TCDD (median 12 parts per trillion (ppt)) than the NIOSH workers (median 75 ppt) when examined in the late 1980s. An analysis was conducted of the combined data sets, adopting a uniform approach to outcome definition, data analysis, and covariate control.
RESULTS—The combined exposed groups did not differ markedly from the combined non-exposed groups for prevalence of diabetes (odds ratio (OR) 1.17, 95% confidence interval (95% CI) 0.92 to 1.48), with no evidence of heterogeneity of exposure effect between studies. Also virtually no difference was found between combined exposed and non-exposed groups in mean fasting serum glucose (difference in log serum glucose 0.002, 95% CI −0.006 to 0.010), and there was little evidence in either study of a dose-response trend for fasting serum glucose. An increasing trend was found (p=0.0001) in prevalence of diabetes with increased TCDD (at the time of examination or at time of last exposure) among the Ranch Hand population, with excess risk largely confined to the highest 8% of the exposed group (>78 ppt serum TCDD), which had an OR of 3.21 (95% CI 1.81 to 5.72) versus those with <10 ppt TCDD. However, no such positive dose-response was found in the NIOSH population.
CONCLUSIONS—There was little overall evidence that the exposed workers were at higher risk than the non-exposed workers of diabetes or abnormal fasting glucose. However, the Ranch Hand subjects showed a positive dose-response for diabetes, whereas the more highly exposed NIOSH subjects did not. The reason for the difference in diabetes dose-response trends between the two studies is unknown.


Keywords: dioxin; diabetes; TCDD     

Occupational paternal exposure to benzene and risk of spontaneous abortion.

OBJECTIVE--The purpose of this study was to evaluate the risk of spontaneous abortion among the wives of male workers occupationally exposed to benzene. METHODS--The wives of 823 men working in two chemical plants at the time of the study were asked to complete a questionnaire describing their pregnancies. The analysis of the 1739 pregnancies that ended in a spontaneous abortion or a birth is presented. The firms' payroll records provided all workers' employment history, including dates. Benzene exposure, graded at two levels (< 5, > or = 5 ppm), was determined for every job, so that benzene exposure for each worker's entire professional life (at these companies) could be assessed. This information was linked to the dates of the pregnancies reported in the questionnaires to enable the exposure status of each pregnancy to be defined (1270 non-exposed and 274 exposed). The frequency of spontaneous abortion, defined as the number of spontaneous abortions divided by the total of spontaneous abortions and births was evaluated. RESULTS--When adjusted for tobacco consumption, mother's age and pregnancy order, the odds ratio of the association between paternal exposure to approximately 5 ppm of benzene and the risk of spontaneous abortion was close to and statistically not different from unity (OR = 1.1; 95% CI (0.7-1.8). CONCLUSION--In this study paternal exposure to benzene did not increase the risk of spontaneous abortion.     

Evaluation of porphyria cutanea tarda in U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

A cross-sectional medical study was performed to evaluate whether occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-contaminated substances is associated with porphyria cutanea tarda or porphyrinuria. The exposed participants were employed more than 15 years earlier in the manufacture of sodium trichlorophenol and its derivatives. The referent group consisted of individuals with no occupational exposure to phenoxy herbicides. A total of 281 workers and 260 referents participated. The pattern of urinary porphyrin excretion for each participant was assessed to determine if symptomatic or subclinical porphyria cutanea tarda was present. None of the participants were found to have symptomatic porphyria cutanea tarda. No difference was found between workers and referents in the prevalence of subclinical porphyria cutanea tarda (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.19, 4.54). There were also no differences in the risk between workers and referents for an out-of-range urinary uro-porphyrin or coproporphyrin concentration. In conclusion, this study did not find an elevated risk for porphyria cutanea tarda or porphyrinuria among workers with high serum TCDD levels. Our review of the literature indicates that there is insufficient evidence available to convincingly support or refute an association in humans between TCDD exposure and porphyria cutanea tarda or porphyrinuria.     

Induction of P-450 in workers exposed to dioxin.

OBJECTIVES--To examine the effects of occupational exposure to substances contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cytochrome P-4501A2 activity in a cross sectional medical survey. METHODS--The exposed workers had been employed at two chemical plants > 15 years earlier in the manufacture of 2,4, 5-trichlorophenol and its derivatives. The control group consisted of people with no occupational exposure to phenoxy herbicides and who lived within the communities of the exposed workers. A total of 58 workers and 125 unexposed controls participated in the analysis. Cytochrome P-450 activity was assessed with test that measures caffeine metabolites in the urine. A ratio of metabolites of caffeine (CMR) constituted a measure of P-4501A2 activity. RESULTS--Compared with the control group in multivariate logistic regression, raised non-significant associations were found for three of four categories of TCDD in exposed workers (TCDD < 20 pg/g, odds ratio (OR) 1.7, 95% confidence interval (95% CI) 0.6 to 5.0, TCDD 20-66, OR 0.3, 95% CI 0.0 to 1.7; TCDD 67-147, OR 2.3, 95% CI 0.6 to 8.8; TCDD > or = 148, OR 3.1, 95% CI 0.8 to 12.5). We found a strongly significant association of CMR and urinary cotinine, a measure of smoking, and urinary free ethanol. We found weak non-significant associations between P-4501A2 activity and increased serum TCDD among workers. CONCLUSIONS--The absence of an association between serum TCDD and cytochrome P-4501A2 may be due to the size of the study, insensitivity of the CMR to assess cytochrome P-4501A2 activity, or inadequate levels of exposure, although these were among the highest in human groups tested.     

Exposure to phenoxy herbicides and the risk of spontaneous abortion.

The Ontario Farm Family Health Study was designed to assess retrospectively the potential adverse effects of exposure to pesticides on pregnancy. Information on the health and life style of approximately 2,000 farm couples, as well as a history of use of pesticides on the farm, was collected by questionnaire. This analysis focuses on pre- and postconception exposure to phenoxy herbicides and the risk of spontaneous abortion using the complete (to date) pregnancy history for each woman. Preconception exposure (from 3 months before conception to the month of conception) was weakly associated with the risk of spontaneous abortion at <20 weeks' gestation [adjusted odds ratio (OR) = 1.1; 95% confidence interval (CI) = 0.6-1.9]. When the analyses were restricted to spontaneous abortions of <12 weeks, the risk was more than doubled (adjusted OR = 2.5; 95% CI = 1.0-6.4), but the results were sensitive to the cutpoint used. If the husband did not normally wear protective equipment during application, the crude OR for early spontaneous abortions was 5.0 (95% CI = 0.7-36.2). Exposure to phenoxy herbicides during the first trimester was generally not associated with increased risk of spontaneous abortion. The results suggest a possible role of preconception (possibly paternal) exposures to phenoxy herbicides in the risk of early spontaneous abortions.     

Recent dioxin contamination from Agent Orange in residents of a southern Vietnam city

Marked elevation of dioxin associated with the herbicide Agent Orange was recently found in 19 of 20 blood samples from persons living in Bien Hoa, a large city in southern Vietnam. This city is located near an air base that was used for Agent Orange spray missions between 1962 and 1970. A spill of Agent Orange occurred at this air base more than 30 years before blood samples were collected in 1999. Samples were collected, frozen, and sent to a World Health Organization--certified dioxin laboratory for congener-specific analysis as part of a Vietnam Red Cross project. Previous analyses of more than 2200 pooled blood samples collected in the 1990s identified Bien Hoa as one of several southern Vietnam areas with persons having elevated blood dioxin levels from exposure to Agent Orange. In sharp contrast to this study, our previous research showed decreasing tissue dioxin levels over time since 1970. Only the dioxin that contaminated Agent Orange, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was elevated in the blood of 19 of 20 persons sampled from Bien Hoa. A comparison, pooled sample from 100 residents of Hanoi, where Agent Orange was not used, measured blood TCDD levels of 2 parts per trillion (ppt). TCDD levels of up to 271 ppt, a 135-fold increase, were found in Bien Hoa residents. TCDD contamination was also found in some nearby soil and sediment samples. Persons new to this region and children born after Agent Orange spraying ended also had elevated TCDD levels. This TCDD uptake was recent and occurred decades after spraying ended. We hypothesize that a major route of current and past exposures is from the movement of dioxin from soil into river sediment, then into fish, and from fish consumption into people.     

Lung cancer development in primary smelter workers: a nested case-referent study

OBJECTIVE: The objective of this study was to study the impact of work-related exposure to mainly arsenic and lead versus smoking in primary smelter workers developing lung cancer. METHODS: In a cohort of 3979 primary smelter workers, 46 subjects had contracted respiratory malignancies. They were compared with 141 age-matched male referents by conditional logistic regression analysis. RESULTS: Cases showed a significantly higher smoking rate as compared with referents: odds ratio (OR) = 4.0; 95% confidence interval (CI) = 1.6-10.1; P = 0.003. When restricted to smokers (33 cases, 63 referents), the cumulative air arsenic exposure index, but not the lead exposure indices, was significantly higher among the cases: OR = 1.07; 95% CI = 1.02-1.11; P = 0.005. CONCLUSIONS: Cumulative arsenic exposure and smoking were identified as risk factors for the development of lung cancer; lead exposure, however, was not.     

低浓度芳香烃溶剂暴露对自然流产影响的基因多态性研究

目的 探讨女工芳香烃溶剂暴露和细胞色素P450氧化酶MSP1基因和谷胱甘肽S转移酶GSTM1基因的多态性对自然流产的影响。方法 采用回顾性流行病学调查方法。使用统一调查表，由经过培训的调查员在北京燕山地区调查了276个女工，其中有自然流产史者58人，无自然流产史者218人。结果 单因素分析发现；GSTM1缺失基因型可致女工自然流产的危险度显著增加[OR=2.07(95%CI:1.15-3.71)]，但未观察到MSP1基因及芳香烃溶剂暴露对女工自然流产的影响，采用多元Logistic回归模型。经文化程度，年龄，倒班，体重指数，被动吸烟，职业紧张混杂因素调整后，可见GSTM1缺失基因型能显著致女工自然流产危险度增加[OR=2.15(95%CI;1.17-3.98)]。以GSTM1存在基因型和MSP1野生基因型为参照组。采用多元Logistic回归模型。并将文化程度，年龄，倒班，体重指数，被动吸烟，职业紧张混杂因素放入回归模型进行调整，在调整混杂因素前后，与参照组比较，均可见MSP1杂合子/突变基因型合并GSTM1缺失基因型使女工自然流失基因型与MSP1突变纯合子/杂合子基因型之间对自然流产的影响存在相加的联合作用。     

Risk of spontaneous abortion among women exposed to polybrominated biphenyls

Accidental contamination of livestock in Michigan in 1973 with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals in 1976. At the time of enrollment, serum was collected and analyzed for PBBs and polychlorinated biphenyls (PCBs). In 1997, women aged 18 years or older and active in the registry were invited to participate in a telephone interview about their health. Using generalized estimating equations to account for correlated outcomes within the same woman, we assessed the risk of spontaneous abortion among 529 women with 1344 potentially exposed pregnancies. PBB and PCB exposure were not associated with risk of spontaneous abortion after adjusting for maternal age at conception, age at menarche, and prior infertility. Compared to pregnancies with PBB exposure below the limit of detection, those with levels above 2.9 ppb had a non-significant reduced odds of spontaneous abortion (adjusted OR=0.73; 95% CI=0.47-1.13). Compared to pregnancies with PCB exposure below the limit of detection, those with levels above 6.5 ppb had little difference in risk (adjusted OR=0.91; 95% CI=0.59-1.41). Maternal age at conception above 34 years was significantly associated with elevated risk of spontaneous abortion (OR=2.46; 95% CI=1.10-5.49). The effect of prior infertility was of borderline significance (OR=1.52; 95% CI=0.98-2.38). Older age at menarche was associated with decreased risk of spontaneous abortion (adjusted OR=0.58; 95% CI: 0.38-0.89, comparing menarche at 12-13 with menarche <12). Our results do not support an association between exposure to PBBs or PCBs and risk of spontaneous abortion.     

Agent Orange and the Vietnamese: the persistence of elevated dioxin levels in human tissues.

OBJECTIVES. The largest known dioxin contamination occurred between 1962 and 1970, when 12 million gallons of Agent Orange, a defoliant mixture contaminated with a form of the most toxic dioxin, were sprayed over southern and central Vietnam. Studies were performed to determine if elevated dioxin levels persist in Vietnamese living in the south of Vietnam. METHODS. With gas chromatography and mass spectroscopy, human milk, adipose tissue, and blood from Vietnamese living in sprayed and unsprayed areas were analyzed, some individually and some pooled, for dioxins and the closely related dibenzofurans. RESULTS. One hundred sixty dioxin analyses of tissue from 3243 persons were performed. Elevated 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) levels as high as 1832 ppt were found in milk lipid collected from southern Vietnam in 1970, and levels up to 103 ppt were found in adipose tissue in the 1980s. Pooled blood collected from southern Vietnam in 1991/92 also showed elevated TCDD up to 33 ppt, whereas tissue from northern Vietnam (where Agent Orange was not used) revealed TCDD levels at or below 2.9 ppt. CONCLUSIONS. Although most Agent Orange studies have focused on American veterans, many Vietnamese had greater exposure. Because health consequences of dioxin contamination are more likely to be found in Vietnamese living in Vietnam than in any other populations, Vietnam provides a unique setting for dioxin studies.     

Paternal Occupational Lead Exposure and Pregnancy Outcome

Abstract

Self-reported reproductive histories of male employees of a lead-zinc smelter were related to pre-conception measures of lead exposure to examine associations between paternal occupational lead exposure and adverse pregnancy outcome The participants reported 2,021 pregnancies which resulted in 1,684 normal live births, 12 stillbirths, 30, birth defects, 203 spontaneous abortions, and 92 “other” outcomes. Birth defects and stillbirths were combined for the analysis. The risk of a stillbirth or birth defect was elevated for pre-conception employment in a high-lead-exposure compared with a low-lead exposure job (odds ratio = 2.7, 95,% confidence interval = 0.7, 9.6). A similar risk was found for pre-conception blood lead levels of 25–39 μg/dL and ≥40μg/dL when compared With blood lead)level of <25μg/dL(OR = 2.9,95% CI = 0.6, 13.3 and OR = 2.5,95% CI = 0.5,11.6, respecdvely). No association was found between pre-conception lead exposure and spontaneous abortion. A relatively low response rate to the questiollnaire and potentially erroneous reporting of reproductive outcome by male workers are limitations of the study.     

Time to pregnancy among male workers of the reinforced plastics industry in Denmark, Italy and The Netherlands. ASCLEPIOS

OBJECTIVES: The relationship between occupational styrene exposure and male fecundity was examined. METHODS: Among 1560 Danish, Italian, and Dutch reinforced plastics workers, 220 styrene-exposed workers and 382 unexposed referents who had fathered a child were identified. A total of 768 historical styrene measurements conducted in 1970-1996 in the study companies formed the basis for semiquantitative exposure assessment in combination with measurements of urinary styrene metabolite levels. All the subjects were interviewed about work conditions and other factors potentially related to reduced fecundity. Fecundity was measured as the reported time to pregnancy (number of months a couple needed to conceive their youngest child). RESULTS: A statistically nonsignificantly reduced fecundity was observed for the styrene-exposed workers [fecundity ratio 0.79, 95% confidence interval (95% CI) 0.59-1.05]. But no consistent pattern of a detrimental effect on fecundity was found when time to pregnancy was related to worktasks indicating higher styrene exposure levels or semiquantitative or quantitative measures of styrene exposure. The workers with high exposure showed a fecundity ratio of 1.09 (95% CI 0.69-1.72). CONCLUSIONS: It is unlikely that styrene exposure has a strong effect on male fecundity.     

Serum dioxin, testosterone, and subsequent risk of benign prostatic hyperplasia: a prospective cohort study of Air Force veterans

BACKGROUND: Operation Ranch Hand veterans were involved in spraying herbicides, including Agent Orange, during the Vietnam War in 1962-1971; Agent Orange was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been hypothesized that dioxins may be partially responsible for an increase of male reproductive tract disorders such as testicular cancer, cryptorchidism, and hypospadias. OBJECTIVES: In this study, our objective was to assess the effect of serum TCDD concentration on the risk of development of benign prostatic hyperplasia (BPH) and on serum testosterone levels. METHODS: This study was a longitudinal, prospective cohort study made up of U.S. Air Force veterans involved in Operation Ranch Hand. Other Air Force veterans who did not spray herbicides were included as comparisons. BPH was determined by medical record review and by medical examinations conducted during the study. Data were available for 971 Ranch Hand and 1,266 comparison veterans. We investigated the relationship between BPH and serum TCDD level using the Cox proportional hazards models adjusted for testosterone levels, body mass index (BMI), and the percentage change in BMI per year. RESULTS: In univariate and multivariate analyses, the risk of BPH decreased with increasing serum TCDD in the comparison group. The multivariate risk ratio for BPH in the comparison group was 0.84 (95% confidence interval, 0.73-0.98). Excluding men with prostate cancer, inflammatory or other prostatic diseases did not substantially alter the association. Serum testosterone levels were inversely associated with serum TCDD levels in both Ranch Hand and comparison groups. CONCLUSIONS: TCDD exposure at general population levels is associated with a decreasing risk of BPH with higher exposure levels. TCDD exposure is also negatively associated with serum testosterone levels.