Suppression of T cells by mesenchymal and cardiac progenitor cells is partly mediated via extracellular vesicles.

Adverse remodeling after myocardial infarction (MI) is strongly influenced by T cells. Stem cell therapy after MI, using mesenchymal stem cells (MSC) or cardiomyocyte progenitor cells (CMPC), improved cardiac function, despite low cell retention and limited differentiation. As MSC secrete many factors affecting T cell proliferation and function, we hypothesized the immune response could be affected as one of the targets of stem cell therapy. Therefore, we studied the immunosuppressive properties of human BM-MSC and CMPC and their extracellular vesicles (EVs) in co-culture with activated T cells. Proliferation of T cells, measured by carboxyfluorescein succinimidyl ester dilution, was significantly reduced in the presence of BM-MSC and CMPC. The inflammatory cytokine panel of the T cells in co-culture, measured by Luminex assay, changed, with strong downregulation of IFN-gamma and TNF-alpha. The effect on proliferation was observed in both direct cell contact and transwell co-culture systems. Transfer of conditioned medium to unrelated T cells abrogated proliferation in these cells. EVs isolated from the conditioned medium of BM-MSC and CMPC prevented T cell proliferation in a dose-dependent fashion. Progenitor cells presence induces up- and downregulation of multiple previously unreported pathways in T cells. In conclusion, both BM-MSC and CMPC have a strong capacity for in vitro immunosuppression. This effect is mediated by paracrine factors, such as extracellular vesicles. Besides proliferation, many additional pathways are influenced by both BM-MSC and CMPC.

Heart Failure in Chronic Myocarditis: A Role for microRNAs?

Myocarditis is an inflammatory disease of the heart, which can persist over a long time. During this time, known as the chronic phase of myocarditis, ongoing inflammation damages the cardiomyocytes. The loss of cardiac cells culminates in the development of dilated cardiomyopathy, often followed by non-ischemic heart failure due to diminished cardiac function. During the course of the disease, expression levels of non-coding small RNAs, called microRNAs (miRNAs), change. Although mainly studied in the acute setting, some of these changes in expression level appear to persist in the chronic phase. In addition to being a much-needed diagnostic tool, these miRNA could provide new treatment options. miRNA-based intervention strategies already showed promising results in the treatment of ischemic cardiovascular diseases in preclinical animal models. By implementing more knowledge on the role of miRNAs in the progression towards heart failure, this can potentially be used in the development of miRNA-based therapeutic interventions in the treatment of myocarditis and thereby preventing the progression towards heart failure. The first part of this review will focus on the natural course of myocarditis and the progression towards heart failure. Secondly, we will discuss the current knowledge on alterations of miRNA expression patterns, and suggest some possible future interventions.

Circulating microRNAs as novel biomarkers for the early diagnosis of acute coronary syndrome.

Small non-coding microRNAs (miRNAs) are important physiological regulators of post-transcriptional gene expression. miRNAs not only reside in the cytoplasm but are also stably present in several extracellular compartments, including the circulation. For that reason, miRNAs are proposed as diagnostic biomarkers for various diseases. Early diagnosis of acute coronary syndrome (ACS), especially non-ST elevated myocardial infarction and unstable angina pectoris, is essential for optimal treatment outcome, and due to the ongoing need for additional identifiers, miRNAs are of special interest as biomarkers for ACS. This review highlights the nature and cellular release mechanisms of circulating miRNAs and therefore their potential role in the diagnosis of myocardial infarction. We will give an update of clinical studies addressing the role of circulating miRNA expression after myocardial infarction and explore the diagnostic value of this potential biomarker.

Cardiac stem cell therapy to modulate inflammation upon myocardial infarction.

BACKGROUND: After myocardial infarction (MI) a local inflammatory reaction clears the damaged myocardium from dead cells and matrix debris at the onset of scar formation. The intensity and duration of this inflammatory reaction are intimately linked to post-infarct remodeling and cardiac dysfunction. Strikingly, treatment with standard anti-inflammatory drugs worsens clinical outcome, suggesting a dual role of inflammation in the cardiac response to injury. Cardiac stem cell therapy with different stem or progenitor cells, e.g. mesenchymal stem cells (MSC), was recently found to have beneficial effects, mostly related to paracrine actions. One of the suggested paracrine effects of cell therapy is modulation of the immune system. SCOPE OF REVIEW: MSC are reported to interact with several cells of the immune system and could therefore be an excellent means to reduce detrimental inflammatory reactions and promote the switch to the healing phase upon cardiac injury. This review focuses on the potential use of MSC therapy for post-MI inflammation. To understand the effects MSC might have on the post-MI heart the cellular and molecular changes in the myocardium after MI need to be understood. MAJOR CONCLUSIONS: By studying the general pathways involved in immunomodulation, and examining the interactions with cell types important for post-MI inflammation, it becomes clear that MSC treatment might provide a new therapeutic opportunity to improve cardiac outcome after acute injury. GENERAL SIGNIFICANCE: Using stem cells to target the post-MI inflammation is a novel therapy which could have considerable clinical implications. This article is part of a Special Issue entitled Biochemistry of Stem Cells.

Adjustment for temporal confounders in a reanalysis of a case-control study of beryllium and lung cancer.

OBJECTIVES: To evaluate potential confounding of the association between beryllium and lung cancer in a reanalysis of data from a published case-control study of workers at a beryllium processing facility. METHODS: The association of cumulative and average beryllium exposure with lung cancer among 142 cases and five age-match controls per case was reanalysed using conditional logistic regression. Adjustment was made independently for potential confounders of hire age and birth year. Alternative adjustments to avoid taking the logarithm of zero were explored. RESULTS: Adjustment for either birth cohort or hire age (two highly correlated factors) attenuated lung cancer risk associated with cumulative exposure; however, lung cancer risk was significantly associated with average exposure using a 10-year lag following adjustment. Stratification of analyses by birth cohort found greater lung cancer risk from cumulative and average exposure for workers born before 1900 than for workers born later. The magnitude of the association between lung cancer and average exposure was not reduced by modifying the method used to take the log of exposure. CONCLUSION: In this reanalysis, average, but not cumulative, beryllium exposure was related to lung cancer risk after adjustment for birth cohort. Confounding by birth cohort is likely related to differences in smoking patterns for workers born before 1900 and the tendency for workers hired during the World War II era to have been older at hire.

Fungicide application practices and personal protective equipment use among orchard farmers in the agricultural health study.

Fungicides are routinely applied to deciduous tree fruits for disease management. Seventy-four private orchard applicators enrolled in the Agricultural Health Study participated in the Orchard Fungicide Exposure Study in 2002-2003. During 144 days of observation, information was obtained on chemicals applied and applicator mixing, application, personal protective, and hygiene practices. At least half of the applicators had orchards with <100 trees. Air blast was the most frequent application method used (55%), followed by hand spray (44%). Rubber gloves were the most frequently worn protective equipment (68% mix; 59% apply), followed by respirators (45% mix; 49% apply), protective outerwear (36% mix; 37% apply), and rubber boots (35% mix; 36% apply). Eye protection was worn while mixing and applying on only 35% and 41% of the days, respectively. Bivariate analyses were performed using repeated logistic or repeated linear regression. Mean duration of mixing, pounds of captan applied, total acres sprayed, and number of tank mixes sprayed were greater for air blast than for hand spray (p < 0.05). Spraying from a tractor/vehicle without an enclosed cab was associated with wearing some type of coverall (p < 0.05). Applicators often did not wash their hands after mixing (77%), a finding not explained by glove use. Glove use during mixing was associated with younger age, while wearing long-sleeve shirts was associated with older age (p < 0.05 each). Self-reported unusually high fungicide exposures were more likely on days applicators performed repairs (p < 0.05). These data will be useful for evaluating fungicide exposure determinants among orchard applicators.

An epidemiological appraisal instrument - a tool for evaluation of epidemiological studies.

In recent years, ergonomics practices have increasingly relied upon the knowledge derived from epidemiological studies. In this regard, there is limited research devoted to the exclusive evaluation of the methodological qualities of ergonomics epidemiological studies. The aim of this study was to develop and test a general purpose 'epidemiological appraisal instrument' (EAI) for evaluating the methodological quality of existing or new ergonomic epidemiological studies using a critical appraisal system rooted in epidemiological principles. A pilot EAI version was developed and tested by a team of epidemiologists/physicians/biostatisticians, with the team leader being both epidemiologist and ergonomist. The pilot version was further tested with regard to other raters with/without a background in epidemiology, biostatistics and ergonomics. A revised version was evaluated for criterion validity and reliability. An assessor with a basic background in epidemiology and biostatistics would be able to correctly respond on four out of five questions, provided that subject matter expertise is obtained on specific items. This may improve with the article's quality. Training may have an effect upon assessors with virtually no background in epidemiology/biostatistics, but with a background in ergonomics. In this latter case, the inter-rater degree of agreement is largely above 90% and assessors can resolve their differences in a subsequent round. The EAI proved to be a valid and reliable appraisal instrument that may be used in various applications, such as systematic reviews and meta-analyses.

Dermal, inhalation, and internal exposure to 1,6-HDI and its oligomers in car body repair shop workers and industrial spray painters.

OBJECTIVES: To study inhalation and dermal exposure to hexamethylene diisocyanate (HDI) and its oligomers as well as personal protection equipment (PPE) use during task performance in conjunction with urinary hexamethylene diamine (HDA) in car body repair shop workers and industrial spray painters. METHODS: Personal task based inhalation samples (n = 95) were collected from six car body repair shops and five industrial painting companies using impingers with di-n-butylamine (DBA) in toluene. In parallel, dermal exposure was assessed using nitril rubber gloves. Gloves were submerged into DBA in toluene after sampling. Analysis for HDI and its oligomers was performed by LC-MS/MS. Urine samples were collected from 55 workers (n = 291) and analysed for HDA by GC-MS. RESULTS: Inhalation exposure was strongly associated with tasks during which aerosolisation occurs. Dermal exposure occurred during tasks that involve direct handling of paint. In car body repair shops associations were found between detectable dermal exposure and glove use (odds ratio (OR) 0.22, 95% confidence interval (CI) 0.09 to 0.57) and inhalation exposure level (OR 1.34, 95% CI 0.97 to 1.84 for a 10-fold increase). HDA in urine could be demonstrated in 36% and 10% of car body repair shop workers and industrial painting company workers respectively. In car body repair shops, the frequency of detectable HDA was significantly elevated at the end of the working day (OR 2.13, 95% CI 1.07 to 4.22 for 3-6 pm v 0-8 am). In both branches HDA was detected in urine of approximately 25% of the spray painters. In addition HDA was detected in urine of a large proportion of non-spray painters in car body repair shops. CONCLUSION: Although (spray) painting with lacquers containing isocyanate hardeners results in the highest external exposures to HDI and oligomers, workers that do not perform paint related tasks may also receive a considerable internal dose.

Mortality analyses in a cohort of 18 235 ethylene oxide exposed workers: follow up extended from 1987 to 1998.

AIMS: To extend mortality follow up from 1987 to 1998 for cohort of 18 235 men and women exposed to ethylene oxide. METHODS: Standard mortality follow up, life table and Cox regression analysis. RESULTS: There were 2852 deaths, compared with 1177 in the earlier 1987 follow up. There was no overall excess of haematopoietic cancers combined or of non-Hodgkin's lymphoma. However, internal exposure-response analyses found positive trends for haematopoietic cancers which were limited to males (15 year lag). The trend in haematopoietic cancer was driven by lymphoid tumours (non-Hodgkin's lymphoma, myeloma, lymphocytic leukaemia), which also have a positive trend with cumulative exposure for males with a 15 year lag. Haematopoietic cancer trends were somewhat weaker in this analysis than trends in the earlier follow up, and analyses restricted to the post-1987 data did not show any significant positive trends (exposure levels dropped sharply in the early 1980s). Breast cancer did not show any overall excess, although there was an excess in the highest cumulative exposure quartile using a 20 year lag. Internal exposure-response analyses found positive trend for breast cancer using the log of cumulative exposure with a 20 year lag. CONCLUSIONS: There was little evidence of any excess cancer mortality for the cohort as a whole, with the exception of bone cancer based on small numbers. Positive exposure-response trends for lymphoid tumours were found for males only. Reasons for the sex specificity of this effect are not known. There was also some evidence of a positive exposure-response for breast cancer mortality.

A participatory approach to the study of lifting demands and musculoskeletal symptoms among Hong Kong workers.

AIMS: To investigate the use of a worker based methodology to assess the physical stresses of lifting tasks on effort expended, and to associate this loading with musculoskeletal outcomes (MO). METHODS: A cross sectional study was conducted on 217 male manual handling workers from the Hong Kong area. The effects of four lifting variables (weight of load, horizontal distance, twisting angle, and vertical travel distance) on effort were examined using a linguistic approach (that is, characterising variables in descriptors such as "heavy" for weight of load). The numerical interpretations of linguistic descriptors were established. In addition, the associations between on the job effort and MO were investigated for 10 body regions including the spine, and both upper and lower extremities. RESULTS: MO were prevalent in multiple body regions (range 12-58%); effort was significantly associated with MO in 8 of 10 body regions (odds ratios with age adjusted ranged from 1.31 for low back to 1.71 for elbows and forearm). The lifting task variables had significant effects on effort, with the weight of load having twice the effect of other variables; each linguistic descriptor was better described by a range of numerical values rather than a single numerical value. CONCLUSIONS: The participatory worker based approach on musculoskeletal outcomes is a promising methodology. Further testing of this approach is recommended.

What is a demanding lifting job for manual handling workers in Hong Kong?

Although lifting tasks are traditionally evaluated by researchers, through the use of methods which depend on one or more approaches (i.e., psychophysical, biomechanical and physiological methods), none of these approaches makes use of expert workers in the evaluation of lifting activities. Given that 97% of lower back symptoms are aches, pains and discomfort and rely on self-reports, it is intuitive to use expert workers in evaluating the stressfulness of lifting activities. In this investigation, 217 workers from three industries in the Hong Kong area were surveyed to determine what constitutes a demanding lifting job from a worker standpoint. This was achieved by asking workers to map, in numerical terms, the level of lifting task parameter described in linguistic values. For example, the weight of load was described in three linguistic descriptors, namely, 'light', 'moderate' and 'heavy'. Then, each worker was asked to assess the meaning of these linguistic descriptors in numerical terms, based on their perception and experience with manual handling work. In this study, workers were asked to map the physical analogue of linguistic descriptors for seven lifting task parameters which are utilized in the NIOSH lifting equation, that is, weight of load, horizontal distance, vertical travel distance, vertical origin of lift, angle of asymmetry, frequency of handling and task duration. The data obtained from the workers were then subjected to validity testing in relation to norms and values reported in the published literature. On a preliminary basis, it appears that workers' assessments are logical and valid. The results suggest that the worker-based methodology is a promising approach and that it is worthwhile to pursue this approach further in the evaluation of industrial lifting activities.

Expression of group IIa secretory phospholipase A2 increases with prostate tumor grade.

PURPOSE: Arachidonate release contributes to prostate tumor progression as arachidonate is metabolized into prostaglandins and leukotrienes, potent mediators of immune suppression, cellular proliferation, tumor motility, and invasion. The group IIa sPLA2 (sPLA2-IIa) can facilitate arachidonate release from cellular phospholipids. We therefore sought to determine whether sPLA2-IIa expression might be related to the development or progression of prostatic adenocarcinoma (CaP). EXPERIMENTAL DESIGN: sPLA2-IIa expression was examined by Western blot analyses of CaP cells and xenografts and by immunohistochemistry of benign prostatic hyperplasias and primary human CaPs (n = 101) using a sPLA2-IIa-specific polyclonal antibody. RESULTS: sPLA2-IIa expression was increased dramatically in the androgen-independent CWR-22R and LNAI CaP cells versus the androgen-dependent CWR-22 and LNCaP cells. Immunohistochemical analyses revealed that sPLA2-IIa expression was also significantly increased with CaP development and advancing disease (trend analysis; Pearson correlation coefficient, P = 0.016). High-grade CaPs showed intense, uniform staining for sPLA2-IIa that was significantly different from that in adjacent benign prostatic hyperplasias (Fisher's exact test, P = 0.021) or low-grade CaP (P = 0.013), both of which showed only focal or weak sPLA2-IIa staining. Further, uniform sPLA2-IIa expression was directly related to the increased proliferative index that typifies advancing disease (P = 0.001). Most significantly, enhanced sPLA2-IIa expression was inversely related to 5-year patient survival (P = 0.015). CONCLUSIONS: These data show that sPLA2-IIa expression increases with progression to androgen-independence and is highest in the most poorly-differentiated, highest-grade primary human CaP samples.

Spontaneous abortion, sex ratio, and paternal occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

There is conflicting research regarding an association between fetal death and paternal exposure to Agent Orange, a phenoxy herbicide widely used in Vietnam that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Men who worked in the U.S. factories that produced Agent Orange were exposed to TCDD at levels hundreds of times higher than TCDD levels in the general population. Wives of TCDD-exposed chemical workers and wives of nonexposed neighborhood referents were interviewed to determine reproductive history. Paternal serum TCDD level at time of conception was estimated for each pregnancy using serum samples taken in 1987. Estimated TCDD levels of workers during or after exposure were high (median, 254 ppt; range, 3-16,340 ppt) compared to referent levels (median, 6 ppt; range, 2-19 ppt). No association between paternal TCDD level at the time of conception and spontaneous abortion was observed among pregnancies fathered by workers with TCDD levels of < 20 ppt [odds ratio (OR) = 0.77; 95% confidence interval (CI), 0.48-1.22], 20 to < 255 ppt (OR = 0.81; 95% CI, 0.40-1.63), 255 to < 1,120, (OR = 0.69; 95% CI, 0.30-1.58), and >or= 1,120 ppt (OR = 0.95; 95% CI, 0.42-2.17) compared to pregnancies fathered by referents. The sex ratio [males/(males + females)] of offspring also did not differ by TCDD exposure (0.53 and 0.54 among workers and referents, respectively). We did not find an association between paternal serum TCDD level and spontaneous abortion or sex ratio of offspring in this population. The estimated TCDD levels in this exposed worker population were much higher than in other studies, providing additional evidence that paternal TCDD exposure does not increase the risk of spontaneous abortion at levels above those observed in the general population. The study could not evaluate the effect of father's childhood or prenatal TCDD exposure on subsequent sex ratio.

Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry.

Although vinyl chloride is an established cause of liver angiosarcoma, the evidence is inconclusive on whether it also causes other neoplastic and nonneoplastic chronic liver diseases as well as neoplasms in other organs. Furthermore, the shape of the dose-response relation for angiosarcoma is uncertain. We have extended for approximately 8 years the mortality and cancer incidence follow-up of 12,700 male workers in the vinyl chloride industry in four European countries. All-cause mortality was lower than expected, whereas cancer mortality was close to expected. A total of 53 deaths from primary liver cancer (standardized mortality ratio 2.40, 95% confidence interval = 1.80-3.14) and 18 incident cases of liver cancer were identified, including 37 angiosarcomas, 10 hepatocellular carcinomas, and 24 liver cancers of other and unknown histology. In Poisson regression analyses we observed a marked exposure response for all liver cancers, angiosarcoma, and hepatocellular carcinoma. The exposure-response trend estimated for liver cancer in analyses restricted to cohort members with cumulative exposures of <1,500 parts per million-years was close to that estimated for the full cohort (relative risk of 2.0 per logarithmic unit of cumulative dose). No strong relation was observed between cumulative vinyl chloride exposure and other cancers. Although cirrhosis mortality was decreased overall, there was a trend with cumulative exposure.

Evaluation of a portable blood lead analyzer with occupationally exposed populations.

BACKGROUND: This project evaluated a portable electroanalytical instrument that is used to rapidly analyze blood lead levels in individuals, using a fresh whole blood sample (venous). METHODS: Samples were obtained from 208 lead-exposed employees who donated two 2 ml venous blood samples into "lead-free" evacuated tubes. One blood sample was analyzed onsite using the portable field instrument while the second sample was analyzed using graphite furnace atomic absorption spectrometry (GFAAS). RESULTS: According to GFAAS results, employee venous blood lead levels ranged from 1 microg/dl to 42 microg/dl. The mean difference between the results from the field instrument and GFAAS was less than 1 microg/dl. Analysis indicates that the results from the field instrument yielded a slight positive bias overall (P value = 0.0213), with less bias for blood lead levels above 10 microg/dl (P value = 0.0738). CONCLUSIONS: Within the blood range evaluated (1-42 microg/dl), the instrument performed adequately according to Clinical Laboratory Improvements Amendments (CLIA) proficiency requirements. The ability of the instrument to perform rapid analysis makes it potentially valuable to occupational health professionals for medical monitoring or on-site investigations.

Risk assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on an epidemiologic study.

The International Agency for Research on Cancer (Lyon, France) recently concluded that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a human carcinogen. There have been few human studies and risk assessments with quantitative exposure data. The authors previously conducted exposure-response analyses based on estimated external TCDD exposure for 3,538 US male chemical workers and found a positive trend for all cancer with increasing cumulative exposure. In the present study, 1988 data from 170 workers with both estimated external exposure and known serum TCDD levels were used to derive the relation between the two. This derived relation was used to estimate serum TCDD levels over time for all 3,538 workers, and new dose-response analyses were conducted by using cumulative serum level. A positive trend (p = 0.003) was found between estimated log cumulative TCDD serum level and cancer mortality. For males, the excess lifetime (75 years) risk of dying of cancer given a TCDD intake of 1.0 pg/kg of body weight per day, twice the background intake, was an estimated 0.05-0.9% above a background lifetime risk of cancer death of 12.4%. Data from this cohort are consistent with another epidemiologic risk assessment from Germany and support recent conclusions by the US Environmental Protection Agency.

Integrin-linked kinase expression increases with prostate tumor grade.

PURPOSE: Integrin-linked kinase (ILK) overexpression can suppress anoikis, promote anchorage-independent cell cycle progression, and induce tumorigenesis and invasion. Inhibition of ILK in prostatic adenocarcinoma (CaP) cells elicits cell cycle arrest and induces apoptosis. Furthermore, ILK expression increases with androgen-independent progression of human CaP cell lines, suggesting that increased ILK expression may be associated with CaP progression. EXPERIMENTAL DESIGN: To assess whether ILK expression may be related to CaP development and/or progression, we have evaluated ILK expression by immunohistochemistry in 100 human prostate tissues. RESULTS: We show that ILK expression increases significantly with CaP progression. ILK immunostaining is specifically increased in high-grade, primary human CaP relative to adjacent benign prostatic hyperplasia (P < 0.001), benign prostatic hyperplasia from patients without cancer (P < 0.002), and low-grade CaP (P = 0.003). ILK overexpression is specifically associated with the increased proliferative index (P = 0.001) that typifies CaP progression. Strikingly, intense uniform ILK immunostaining was inversely related to 5-year patient survival (P = 0.004). CONCLUSIONS: ILK expression increases dramatically with CaP progression. ILK expression is also specifically related to the disproportionately increased proliferative index that contributes to the net gain of CaP cells during progression. Finally, enhanced ILK expression is inversely related to 5-year patient survival. These data therefore implicate increased ILK expression in prostate tumor progression.

Determinants of chlorpyrifos exposures and urinary 3,5,6-trichloro-2-pyridinol levels among termiticide applicators.

The exposures and work activities of 41 applicators in North Carolina using chlorpyrifos-containing termiticides were characterized. Personal air and urine samples were collected on multiple days within one week. Detailed information about chemical use, tasks, personal protective equipment and hygiene was recorded. During the 202 applicator-days monitored, 415 treatment jobs were performed. Full-shift chlorpyrifos exposures ranged from <0.048 to 110 microg/m(3) (N=184), with a geometric mean (GM) of 10 microg/m(3). Urinary 3,5,6-trichloro-2-pyridinol (TCP) levels ranged from 9.42 to 1960 microg/g creatinine (N=271) and varied significantly by day of the week (GM range: 169-262 microg/g creatinine). Predictive models for chlorpyrifos air exposure and urinary TCP levels were developed using mixed-effects stepwise linear regression. Determinants of airborne chlorpyrifos exposure included minutes chlorpyrifos applied and enclosed crawl space treated (yes/no). Determinants of TCP levels (depending on the model) included day-of-the-week, the chlorpyrifos air concentration one and two days before urine collection, minutes of chlorpyrifos applied one and two days before urine collection, enclosed crawl space treated (yes/no), and commercial structure treated (time-weighted). Within- and between-worker variability was similar for airborne chlorpyrifos; however, for TCP, between-worker variability exceeded within-worker variability by six times. The elimination half-life of TCP (26.9 h) and possibly the short sampling interval (one week) may explain the low TCP within-worker variability. Applicators' weekly mean ln(TCP levels) and weekly mean ln(chlorpyrifos air concentrations) were highly and positively linearly correlated (r(2)=0.73, P<0.0001). In summary, mixed-effects models were successfully constructed to predict airborne chlorpyrifos exposure and urinary TCP levels.