Objective: The aim of this study was to describe a study of medical monitoring methods and lessons learned in detecting health outcomes in U.S. plants producing toluene diisocyanate (TDI). Methods: A multidisciplinary team implemented a medical and environmental monitoring program in three TDI plants. Results: Of 269 eligible workers, 197 (73%) participated and 42 (21%) met symptom and/or lung function criteria that would trigger evaluation for possible asthma over 5 years of data collection. Subsequent evaluation was delayed for most, and a web-based data collection system improved timeliness. Conclusion: Medical monitoring of TDI workers identified workers triggering further assessment per study protocol. Systems and/or personnel to ensure rapid follow-up are needed to highlight when triggering events represent potential cases of asthma needing further evaluation. Implementation of a research protocol requires resources and oversight beyond an occupational health program.

Objective: This study examines asthma risk in facilities producing toluene diisocyanate (TDI). Methods: A total of 197 workers were monitored from 2007 to 2012. TDI air concentrations were used to estimate exposures. Results: The incidence of cases consistent with TDI-induced asthma was 0.009 per person-years (seven cases) or consistent with TDI-induced asthma or asthma indeterminate regarding work-relatedness was 0.012 (nine cases). Increased risk of cases consistent with TDI asthma was observed for cumulative (odds ratio [OR] = 2.08, 95% confidence interval [CI] 1.07 to 4.05) per logarithm parts per billion-years and peak TDI exposures (OR = 1.18, 95% CI 1.06 to 1.32) (logarithm parts per billion). There was a weak association with cumulative and peak exposures for decline of short-term forced expiratory volume in one second (FEV1). Asthma symptoms were associated with workers noticing an odor of TDI (OR 6.02; 95% CI 1.36 to 26.68). Conclusions: There is evidence that cumulative and peak exposures are associated with TDI-induced asthma.

OBJECTIVE:The aim of this study was to investigate lung function among toluene diisocyanate (TDI) production workers.METHODS:One hundred ninety-seven U.S workers performed spirometry from 2006 through 2012. Results were compared within the study cohort and with U.S. population measures. A mixed-effects model assessed factors affecting repeated forced expiratory volume in 1 second (FEV1) measurements.RESULTS:The cohort's mean FEV1 and forced vital capacity (FVC) percent reference values, although greater than 90%, were significantly lower and the prevalence of abnormal spirometry (predominantly restrictive pattern) was significantly higher than in the U.S.POPULATION:Differences in lung function among workers with higher cumulative TDI exposure were in the direction of an exposure effect, but not significant.CONCLUSION:We found little evidence of an adverse effect of TDI exposure on longitudinal spirometry in these workers. The association between TDI exposure and the increasing prevalence of a restrictive pattern needs further exploration.

Objective: In 2004, The American Chemistry Council Phosgene Panel established a phosgene exposure registry among US phosgene producers with the primary purpose of monitoring health outcome information for workers with acute exposure. Methods: We examine symptoms among 338 workers with phosgene exposure. The phosgene exposures averaged 8.3 ppm-minutes ranging up to 159 ppm-minutes with most exposures below 10 ppm-minutes. Results: We found that the level of phosgene exposure in ppm-minutes was related to workers reporting mostly irritation symptoms of the nose, throat and eyes within 48 hours of exposure. However, we found no relationship between phosgene exposure and the presence of symptoms 30 days after exposure. Conclusions: These findings lend credence to the theory that prolonged respiratory effects do not occur with doses less than 150 ppm-minutes.

[Objective]To determine if serum dioxin levels are higher among trichlorophenol (TCP) or pentachlorophenol (PCP) workers with and without chloracne and to examine characteristics of workers with chloracne.[Methods]We collected blood from 26 PCP workers,12 TCP workers,and 36 workers with no PCP or TCP exposure and measured dioxin levels.Chloracne was determined by examining plant medical records.[Results]We observed higher serum levels of the toxic equivalency (according to the World Health Organization) based on 2378-TCDD for 12378-PeCDD,123678-H6CDD,123789-H6CDD,and 123678-H6CDF among the PCP workers with chloracne compared to the PCP workers with no chloracne.There were no significant differences in serum levels for the TCP workers by chloracne status,although the 2378-TCDD levels were higher among the participants who previously had chloraene (43.6 ppt vs.16.4 ppt).The putative risk factors for chloraene of younger age at first exposure and more years since first exposure were observed in the TCP workers but not the PCP workers.Chloracne in the PCP workers was associated with longer duration of exposure prior to the diagnosis.[Conclusion]Chloracne is a good indicator for high dioxin exposures,and TCP and PCP workers have distinctively different serum profiles of dioxin congeners.

BACKGROUND Hydroxypropylmethylcellulose (HPMC) is a modified cellulose fiber that creates a viscous solution in the gastrointestinal tract. The present study examined the dose-response characteristics of high-viscosity (HV)-HPMC consumption on postprandial glucose and insulin levels in men and women at increased risk for type 2 diabetes mellitus. METHODS Subjects were a subset of participants in two trials with elevated peak postprandial glucose [>or=7.8 mmol/L (>or=140 mg/dL)] and body mass index (BMI) >or=27 kg/m(2). Subjects (n = 39) consumed breakfast meals containing 75 g of carbohydrate, each of which contained 1, 2, 4, or 8 g of HV-HPMC or a cellulose control in a randomized, double-blind manner. Each subject completed tests with control and two HV-HPMC doses. RESULTS Peak glucose concentration was lower than control (all P < 0.01) following 2 g (10%), 4 g (18%), and 8 g (20%) of HV-HPMC. Peak insulin was also reduced (P < 0.01) following 2 g (32%), 4 g (35%), and 8 g (46%) of HV-HPMC doses versus control. Incremental areas for glucose from 0 to 120 min were reduced by 8-40% versus control but only reached significance for the 4-g and 8-g conditions, whereas incremental areas under the insulin curves were reduced by 14-53% (P < 0.01 for 2, 4, and 8 g of HV-HPMC). CONCLUSIONS Among subjects at risk for type 2 diabetes mellitus, 1.0-8.0 g of HV-HPMC blunted postprandial glucose and insulin responses in a dose-dependent manner. Additional research is warranted to assess whether chronic consumption might retard the development or progression of glucose intolerance.

BACKGROUND: Hydroxypropylmethylcellulose (HPMC), a viscous, soluble dietary fiber, has been shown to be efficacious for lowering total and low-density lipoprotein cholesterol (LDL-C) concentrations. The relative effects of various dosages and viscosities of HPMC have not been fully evaluated.OBJECTIVE: To examine the lipid-altering effects of several formulations of HPMC.METHODS: In this randomized, double-blind pilot study, 165 men and women with primary hypercholesterolemia consumed a control product (snack bar or drink mix) or an HPMC-containing test bar or drink for 4 weeks. HPMC-containing products delivered 3, 5, or 10 g of HPMC of low, moderate, moderately high, or high viscosity (9 HPMC groups, each with similar to 15 subjects).RESULTS: Data from drink and bar groups were combined because there was no evidence of a vehicle effect. The resulting analysis included data from the control and 6 HPMC dose and viscosity combinations. All HPMC groups showed LDL-C reductions ranging from 6.1 to 13.3% (P < .05 vs. baseline for 6 of the 7 groups), compared with a nonsignificant reduction (1.9%) in the control group. Changes in total and non-high-density lipoprotein cholesterol paralleled those for LDL-C. Concentrations of high-density lipoprotein cholesterol, triglycerides, apolipoprotein 13, and high-sensitivity C-reactive protein were not significantly altered.CONCLUSION: This pilot study provides preliminary evidence to support the efficacy of various formulations of HPMC for reducing cholesterol carried by atherogenic particles in men and women with primary hypercholesterolemia. Additional research will be required to more clearly define the roles of viscosity and dosage on the lipid-altering effects of HPMC. (C) 2009 National Lipid Association. All rights reserved.

We evaluated serum concentrations of five selected dioxin, furan, and polychlorinated biphenyls (PCB) congeners among 412 workers at a Midland, Michigan plant that manufactured trichlorophenol and pentachlorophenol (PCP) and formulated chlorophenol-based products. We examined occupational indicators of exposure to these chlorophenols taking into account intrinsic factors such as age and body fat and potential environmental sources of exposure from consumption of local game and fish and other occupations. All five congeners were significantly associated with age and body fat. 2378-TCDD serum concentrations were associated with trichlorophenol operations, total years employed at the plant, as well as working as a hazardous waste worker. 123678-H(6)CDD serum concentrations were related to occupational PCP exposure, chloracne, recent weight loss, eating local game, and working as a hazardous waste worker. Serum concentrations of PCB126 were related to smoking (inversely), and eating local fish or local game. Other factors such as diet and jobs outside of the chlorophenol plant exposures had only a very minor impact on dioxin and furan concentrations in these workers.

Hydroxypropylmethylcellulose (HPMC) and methylcellulose (MC) are modified cellulose dietary fibers that generate viscous solutions in the gastrointestinal (GI) tract. This study assessed the effects of high viscosity (HV) HPMC, ultra-HV (UHV) HPMC, and medium viscosity MC on postprandial glucose and insulin responses in overweight and obese men and women (n = 50). After overnight fasts, subjects consumed 5 breakfast meals containing 75 g carbohydrate, each of which contained 1 of the following: 1 g HV-HPMC, 2 g HV-HPMC, 2 g UHV-HPMC, 4 g medium-viscosity MC or control (2 g cellulose). Test sequence was randomized and double-blind, except the MC test, which was last and single-blind (46 subjects completed all 5 tests). Glucose and insulin responses were determined pre-meal and for 120 min postprandially. Median (interquartile limits) peak glucose concentration was lower (P = 0.001) after the meal containing 2.0 g UHV-HPMC (7.1, 6.3-8.2 mmol/L) compared with the control meal (7.7, 6.6-8.7 mmol/L). The control did not differ from the other conditions for peak glucose or for any of the HPMC/MC conditions for glucose incremental areas under the curves (IAUC). Peak insulin was reduced (P < 0.05) for all HPMC/MC conditions compared with control. Insulin IAUC was lower than control (P < 0.001) after meals containing 2 g HV-HPMC, 2 g UHV-HPMC, and 4 g MC. GI symptoms did not differ among treatments. These findings indicate that HV-HPMC (1 and 2 g), UHV-HPMC (2 g), and MC (4 g) consumption reduced postprandial insulin excursions consistent with delayed glucose absorption.

We examined the serum lipid adjusted levels of 2,3,7,8-substituted chlorinated dioxins and furans, and four coplanar PCBs for 98 workers. We found workers who worked only in the trichlorophenol units had mean lipid adjusted 2,3,7,8-TCDD levels of 36.8ppt significantly higher (p<0.05) than 6.0ppt in the reference group. Workers who worked only in the pentachlorophenol units had mean lipid adjusted levels for 123478-HxCDD of 14.8ppt, 123678-HxCDD of 156.4ppt,123789-HxCDD of 23.7ppt, 1234678-HpCDD of 234.6ppt, and OCDD of 2,778.2ppt significantly higher (p<0.05) than the reference group levels for the same congeners of 7.5, 71.8, 8.0, 67.5, and 483.2ppt, respectively. While we did find 12378-PeCDD levels higher than the reference group in trichlorophenol and pentachlorophenol workers, the differences are small, and could be attributed to normal variation. All furan levels among the trichlorophenol or pentachlorophenol only workers were not significantly different than the reference group. Workers with both trichlorophenol and pentachlorophenol exposures had mean dioxin levels consistent with complex chlorophenol exposures. Tradesmen who worked throughout the plant had congener profiles consistent with both trichlorophenol and pentachlorophenol exposures. PCB 169, 23478-PeCDF, 123478-HxCDF, and 123678-HxCDF levels were also significantly greater (p<0.05) in these tradesmen than in the reference group. We found distinct patterns of dioxin congeners many years after exposure among workers with different chlorophenol exposures. We were effectively able to distinguish past trichlorophenol exposures from pentachlorophenol exposures based on differing serum dioxin profiles among workers.

OBJECTIVE—High-viscosity hydroxypropylmethylcellulose (HV-HPMC) is a modified cellulose fiber that produces a viscous gel in the gastrointestinal tract. Clinical trials demonstrate that consumption of HV-HPMC significantly lowers cholesterol, but limited information has been available on the influence of HV-HPMC on postprandial insulin and glucose responses. The objective of this investigation was to assess the influence of HV-HPMC on postprandial glucose and insulin responses in overweight and obese men and women. RESEARCH DESIGN AND METHODS—Participants were 31 overweight or obese men and women without diabetes who underwent three breakfast meal tests in random order, separated by ≥72 h. Test meals containing 75 g carbohydrate plus 4 or 8 g HV-HPMC or control meals containing 8 g cellulose were delivered in a double-blind fashion. RESULTS—Peak glucose was significantly lower (P < 0.001) after both HV-HPMC–containing meals (7.4 mmol/l [4 g] and 7.4 mmol/l [8 g]) compared with the control meal (8.6 mmol/l). Peak insulin concentrations and the incremental areas for glucose and insulin from 0 to 120 min were also significantly reduced after both HV-HPMC doses versus control (all P < 0.01). CONCLUSIONS—These findings indicate that HV-HPMC consumption reduces postprandial glucose and insulin excursions, which may favorably alter risks for diabetes and cardiovascular disease.

This study examines serum levels of 2,3,7,8-substituted chlorinated dioxins and furans, and PCBs for 375 Michigan workers with potential chlorophenol exposure, 37 Worker Referents, and 71 Community Referents. The chlorophenol workers were last exposed to trichlorophenol and/or pentachlorophenol 26–62 years ago. Employees working only in the trichlorophenol units had mean lipid-adjusted 2378-tetrachlorodibenzo-p-dioxin (TCDD) levels of 15.9 ppt compared with 6.5 ppt in the Worker Referents. Employees working only in the pentachlorophenol units had mean lipid-adjusted levels for 123478-H6CDD of 16.1 ppt, 123678-H6CDD of 150.6 ppt, 123789-H6CDD of 20.2 ppt, 1234678-H7CDD of 192.6 ppt, and OCDD of 2,594.0 ppt compared with the Worker Referent levels for the same congeners of 7.5, 74.7, 8.6, 68.7, and 509.1 ppt, respectively. All furan and PCB levels among workers in the trichlorophenol and/or pentachlorophenol departments were similar to the Worker Referents. The Tradesmen who worked throughout the plant had dioxin congener profiles consistent with both trichlorophenol and pentachlorophenol exposures. PCB levels and levels of 23478-P5CDF, 123478-H6CDF, and 123678-H6CDF were also greater in these Tradesmen than in the Worker Referents. The Worker Referent group had higher levels of dioxins and furans than the Community Referents indicating the potential for exposure outside the chlorophenol departments at the site. Distinct patterns of dioxin congeners were found many years after exposure among workers with different chlorophenol exposures. Furthermore, past trichlorophenol exposures were readily distinguishable from past pentachlorophenol exposures based on serum dioxin evaluations among workers. These data can be used to better assess dioxin exposures in future health studies.

High‐viscosity hydroxypropylmethylcellulose (HV‐HPMC) is a dietary fiber that forms a viscous gel in the gastrointestinal tract after consumption. The aim of the present analysis was to evaluate the influence of glucose tolerance on postprandial responses to HV‐HPMC. Subjects were classified into low (LPG) or high (HPG) subgroups based on the median peak glucose concentration (< or ≥147 mg/dL) after a control test meal containing 75 g of carbohydrate. Those with HPG (n=16) did not differ from the LPG subset (n=15) in demographic characteristics or fasting insulin, but had significantly higher fasting glucose (99 vs. 91 mg/dL, p=0.006). Postprandial glucose (7882 vs. 5122 min x mg/dL, p=0.023) and insulin (5184 vs. 2739 min x mU/L, p=0.019) incremental areas under the curves (IAUC, 0–120 min) were higher in the HPG subjects. Adding HV‐HPMC (4 or 8 g) to the meal reduced glucose and insulin responses (p<0.001). The degree of blunting of the insulin IAUC did not differ between the HPG and LPG subsets (−47 vs. −43%, p=0.671), but the glucose IAUC was blunted to a larger degree in the HPG subjects (−41 vs. −26%, p=0.034). Thus, slowing the rate of glucose absorption with HV‐HPMC had a larger impact on postprandial glycemia in subjects with HPG. These findings may have implications for understanding how slowing carbohydrate absorption may influence diabetes risk.

Several studies have found that current levels of 2,3,7,8 tetrachlorodibenzo-p-dioxin in serum lipids are related to age with older persons generally having higher levels. To account for this age pattern, reference ranges based on national samples have been established in order to allow determination of background levels for regional studies. In several studies, body mass index (BMI), has also been associated with current 2,3,7,8 tetrachlorodibenzo-p-dioxin levels with increasing body mass index related to increasing levels. We measured lipid-adjusted serum levels for all 2,3,7,8-substituted dioxins and furans in 62 chemical manufacturing workers with chlorophenol exposures and 36 workers without chlorophenol exposures employed at the same location. We then assessed the impact of age and BMI on the serum levels of all these compounds in the presence of other potential confounders. We found that both factors are important independent determinants of serum levels of 2,3,7,8-substituted dioxins and furans. Specifically, age and BMI are both important factors for assessing background levels of 2,3,7,8 tetrachlorodibenzo-p-dioxin, 1,2,3,7,8 pentachlorodibenzo-p-dioxin and the calculated total toxic equivalency. BMI, but not age, is important for assessing background levels of higher chlorinated dioxins and some hexachlorofurans. We conclude that age and BMI are both important considerations when comparing a potentially exposed group to a referent group, or to national norms. Further, age and BMI may also be important in epidemiology studies where back-extrapolation from current dioxin levels is used to assess historical chlorophenol exposure.

Using gas chromatography/mass spectrometry, we measured lipid-adjusted serum levels for all 2,3,7,8-substituted dioxins and furans, and four coplanar polychlorinated biphenyls in 62 workers with chlorophenol exposure and 36 workers without chlorophenol exposures working at the same plant during the same time. We oversampled among workers diagnosed with chloracne. Mean dioxin background levels from 36 nonchlorophenol workers were estimated as 6.0 parts-per-trillion (ppt) for 2,3,7,8 tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 67.5 ppt for 1,2,3,4,6,7,8 heptachlorodibenzo-p-dioxin (Hepta-CDD). We found different dioxin and furan profiles for trichlorophenol and pentachlorophenol (PCP) workers. Among trichlorophenol workers with chloracne, we found 2,3,7,8-TCDD ( mean 30.5 ppt) above background levels and among PCP workers with chloracne, we found high levels of Hepta-CDD (mean = 312.5 ppt) and other higher chlorinated dioxins and furans. Cumulative exposure estimates for dioxins for both 2,3,7,8-TCDD and the higher chlorinated dioxins created in the early 1980s for our epidemiology studies were highly correlated with serum dioxin levels when age and body mass index were taken into account. While workers previously diagnosed with chloracne had high serum dioxin levels, some workers without diagnosed chloracne also had high levels. Among tradesworkers with plant-wide responsibilities, we observed serum dioxins and PCB levels higher than background indicating workplace exposures. We estimate that the mean level of 2,3,7,8-TCDD present in the serum of workers on the date workplace exposure terminated was 267 ppt (ranging from 8 to 1184 ppt) assuming a 9-year half-life, 582 ppt ( ranging from 10 to 2,641 ppt) assuming a 7-year half-life, and 1928 ppt (ranging from 22 to 17,847) when a toxicokinetic model is used. We conclude that our findings are consistent with other studies reporting high serum dioxin levels among chlorophenol workers after occupational exposures.

We identified and followed 27,795 Texas-based employees of The Dow Chemical Company from 1940 through 1996. Overall, the study population experienced favorable mortality patterns when compared with external populations. We observed lower death rates for several major causes of death, including heart disease and many cancers, which may be indicative of the "healthy worker effect" and the absence of major health hazards from these manufacturing facilities. Previous studies of the chemical company found higher-than-expected rates of lung, kidney, and brain cancer. More lung cancer deaths than expected continue to occur when the plant population is compared with the US and Texas populations but not with the local 5-county region. The numbers of brain and kidney cancers were also greater than expected, but the risk is attenuating. These findings, taken together with previously reported studies that examined these lung, kidney, and brain cancers relative to exposures to specific hazardous agents, do not suggest an occupational etiology.

We examine death rates among 773 workers exposed to higher chlorinated dioxins in pentachlorophenol manufacture. Vital status was followed from 1940 to 2003. Exposure to 123478-HxCDD, 123678-HxCDD, 123789-HxCDD, 1234678-HpCDD, and OCDD was modeled based on a serum evaluation of 365 of these workers. The number of deaths from all causes combined, all cancers combined, and lung cancer, diabetes, and ischemic heart disease were near expected levels and there was no increasing trend with increasing exposure to the higher chlorinated dioxins. Standardized mortality ratios (SMR) of kidney cancer and stomach ulcers, a concern from a previous study, were lower in the current study. We did observe one soft tissue sarcoma death (SMR=2.2, 95% confidence interval (CI) 0.1-12.1), and 8 deaths from non-Hodgkin's lymphoma (SMR=2.4, 95% CI 1.0-4.8). Other than chloracne and possibly non-Hodgkin's lymphoma, we find little evidence for increased disease risk from exposure to these higher chlorinated dioxins.