Mothball ingestion as a manifestation of pica, leading to paradichlorobenzene CNS toxicity.

BACKGROUND: Pica is a poorly understood psychiatric disorder that presents with the ingestion of non-nutritious substances for unclear reasons. A high index of suspicion for unusual toxin exposure aids in the diagnosis of pica patients presenting with unexplained neurodegenerative features. METHODS: We present a 47-year-old female with worsening gait over the past year. Prior to this, she was fully independent with activities of daily living, but is now mostly housebound due to frequent falls. Past medical history is significant for menorrhagia, iron deficiency anemia and pica. CBC and iron studies revealed iron deficiency with microcytic hypochromic anemia. MRI brain demonstrated symmetrical T2 hyperintensities within the middle cerebellar peduncles. RESULTS: Differential diagnoses for her clinical deficits and imaging, including Spinocerebellar Ataxia, Multiple System Atrophy and Fragile X Tremor-Ataxia Syndrome, were excluded based on neurological assessment, family history and genetic PCR testing. Collateral history revealed a regular habit of mothball ingestion and serum paradichlorobenzene levels were elevated to 15mcg/mL. The patient was treated with iron replacement therapy and her symptoms gradually improved over several months. CONCLUSION: Iron deficiency anemia is commonly associated with pica, which can lead to toxin ingestion. A high index of suspicion for toxin ingestion in pica patients can immensely aid in the diagnosis. Mothball abuse secondary to pica may affect the CNS and can present with nonspecific neurodegenerative changes. To our knowledge, there have been no reported cases in the literature with paradichlorobenzene neurotoxicity predominantly affecting the middle cerebellar peduncles.

Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Population pharmacokinetic methods were used to characterize the pharmacokinetics of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) in patients with chronic obstructive pulmonary disease (COPD) when administered as a fixed-dose combination via a single closed inhaler. METHODS: Plasma concentration data from three studies were analyzed using non-linear mixed-effects modeling in NONMEM®. RESULTS: The pooled dataset consisted of 2948, 2589, and 3331 FF, UMEC, and VI observations from 714, 622, and 817 patients with COPD, respectively. There were 41%, 13%, and 21% of observations below the quantification limit for FF, UMEC, and VI, respectively. The pharmacokinetics of FF, UMEC, and VI were all adequately described by a two-compartment model with first-order absorption. The following covariates were statistically significant, but none were considered to be clinically relevant. For FF, Japanese heritage and FF/VI treatment on apparent inhaled clearance (CL/F) with FF CL/F 35% lower in patients of Japanese heritage across all treatments and FF CL/F 42% higher in patients with COPD following FF/VI administration. This is in line with the product label. For UMEC, weight, age, and smoking status on CL/F and weight on apparent volume of distribution (V2/F) with every 10% increase in age from 60 years of age leading to approximately a 6% decrease in UMEC CL/F and every 10% increase in weight from 70 kg leading to approximately a 6% increase in UMEC CL/F and approximately an 8% increase in UMEC V2/F. For a subject with COPD who smoked, UMEC CL/F was 28% higher. For VI, weight on CL/F and smoking status on V2/F with an approximately 4% increase in VI CL/F for every 10% increase in weight from 70 kg, and for a subject with COPD who smoked, VI V2/F was 46% higher. The majority of these covariates have been previously identified in historical analyses. None of these effects were clinically relevant in terms of systemic exposures and do not warrant dose adjustment. CONCLUSIONS: All FF, UMEC, and VI plasma concentrations were well interspersed with historical data and were all adequately described by a two-compartment model with first-order absorption. There were no clinically relevant differences in FF, UMEC, or VI systemic exposures when administered as FF/UMEC/VI, FF/VI + UMEC, or the dual combinations FF/VI and/or UMEC/VI.

HPLC-UV and spectrofluorimetric methods for simultaneous estimation of fluticasone furoate and vilanterol in rabbit plasma: A pharmacokinetic study.

Fluticasone furoate (FF) and vilanterol trifenatate (VT) is a widely prescribed combination in the management of asthma and chronic obstructive pulmonary disease. In the present study, two quantitative methods based on HPLC-UV and spectrofluorimetric analysis had been developed and validated for simultaneous estimation of FF and VT in rabbit plasma using baclomethasone as internal standard (ISTD). Analytes and ISTD were separated from plasma using simple step of protein precipitation with acetonitrile. Chromatographic separation was achieved on Spherisorb S5 ODS2 (250 mm × 4.6 mm, 5.0 µm) column using mobile phase that constitute acetonitrile-0.01% glacial acetic acid in water (70:30, v/v) and then detected on a UV detector at 235 nm wavelength. Spectrofluorimetric detection was performed using absorption/emission wavelength (λabs/em) of 286/352 nm and 362/407 nm for FF and VT, respectively. For both analytes, linearity ranged from 4-200 ng/mL to 10-200 ng/mL using HPLC-UV and spectrofluorimetric method, respectively. Methods were validated as per FDA recommendations. Statistical analysis revealed that these detection methods are statistically insignificant difference and can be used interchangeably without any bias. Further, these methods were applied in pharmacokinetic study for simultaneous estimation of FF and VT in rabbit plasma.

Blood eosinophils and treatment response with triple and dual combination therapy in chronic obstructive pulmonary disease: analysis of the IMPACT trial.

BACKGROUND: Previous studies have highlighted a relationship between reduction in rate of exacerbations with therapies containing inhaled corticosteroids (ICS) and baseline blood eosinophil count in patients with chronic obstructive pulmonary disease (COPD). The IMPACT trial showed that once-daily single-inhaler triple therapy significantly reduced exacerbations versus dual therapies. Blood eosinophil counts and smoking status could be important modifiers of treatment response to ICS. We aimed to model these relationships and their interactions, including outcomes other than exacerbations. METHODS: IMPACT was a phase 3, randomised, double-blind, parallel-group, 52-week global study comparing once-daily single-inhaler triple therapy (fluticasone furoate-umeclidinium-vilanterol) with dual inhaled therapy (fluticasone furoate-vilanterol or umeclidinium-vilanterol). Eligible patients had moderate-to-very-severe COPD and at least one moderate or severe exacerbation in the previous year. We used fractional polynomials to model continuous blood eosinophil counts. We used negative binomial regression for numbers of moderate and severe exacerbations, severe exacerbations, and pneumonia. We modelled differences at week 52 in trough FEV1, St George's Respiratory Questionnaire (SGRQ) total score, and Transition Dyspnoea Index using repeated measurements mixed effect models. IMPACT was registered with ClinicalTrials.gov, number NCT02164513. FINDINGS: The magnitude of benefit of regimens containing ICS (fluticasone furoate-umeclidinium-vilanterol n=4151 and fluticasone furoate-vilanterol n=4134) in reducing rates of moderate and severe exacerbations increased in proportion with blood eosinophil count, compared with a non-ICS dual long-acting bronchodilator (umeclidinium-vilanterol n=2070). The moderate and severe exacerbation rate ratio for triple therapy versus umeclidinium-vilanterol was 0·88 (95% CI 0·74 to 1·04) at blood eosinophil count less than 90 cells per µL and 0·56 (0·47 to 0·66) at counts of 310 cells per µL or more; the corresponding rate ratio for fluticasone furoate-vilanterol versus umeclidinium-vilanterol was 1·09 (0·91 to 1·29) and 0·56 (0·47 to 0·66), respectively. Similar results were observed for FEV1, Transition Dyspnoea Index, and SGRQ total score; however, the relationship with FEV1 was less marked. At blood eosinophil counts less than 90 cells per µL and at counts of 310 cells per µL or more, the triple therapy versus umeclidinium-vilanterol treatment difference was 40 mL (95% CI 10 to 70) and 60 mL (20 to 100) for trough FEV1, -0·01 (-0·68 to 0·66) and 0·30 (-0·37 to 0·97) for Transition Dyspnoea Index score, and -0·01 (-1·81 to 1·78) and -2·78 (-4·64 to -0·92) for SGRQ total score, respectively. Smoking status modified the relationship between observed efficacy and blood eosinophil count for moderate or severe exacerbations, Transition Dyspnoea Index, and FEV1, with former smokers being more corticosteroid responsive at any eosinophil count than current smokers. INTERPRETATION: This analysis of the IMPACT trial shows that assessment of blood eosinophil count and smoking status has the potential to optimise ICS use in clinical practice in patients with COPD and a history of exacerbations. FUNDING: GlaxoSmithKline.

Human exposure to bisphenol AF and diethylhexylphthalate increases susceptibility to develop differentiated thyroid cancer in patients with thyroid nodules.

Pollutants represent potential threats to the human health, being ubiquitous in the environment and exerting toxicity even at low doses. This study aims at investigating the role of fifteen multiclass organic pollutants, assumed as markers of environmental pollution, most of which exerting endocrine-disrupting activity, in thyroid cancer development. The increasing incidence of differentiated thyroid cancer (DTC) may be related to the rising production and environmental dissemination of pollutants. Fifty-five patients, twenty-seven with diagnosis of benign thyroid nodules and twenty-eight suffering from differentiated thyroid cancer, were enrolled and the concentration levels of seven bisphenols, two phthalates (i.e. di(2-ethylhexyl) phthalate (DEHP) and its main metabolite, mono-(2-ethyl-hexyl) phthalate) (MEHP)), two chlorobenzenes, (1,4-dichlorobenzene and 1,2,4,5-tetrachlorobenzene), and 3 phenol derivatives (2-chlorophenol, 4- nonylphenol, and triclosan) were determined in their serum by using a validated analytical method based on high performance liquid chromatography with ultraviolet tandem fluorescence detection. A significant relationship was found between malignancy and the detection in the serum of both bisphenol AF and DEHP. Indeed, their presence confers a more than fourteen times higher risk of developing differentiated thyroid cancer. Relationship between these two pollutants and the risk of malignancy was dose-independent and not mediated by higher thyroid stimulating hormone levels. Even if a conclusive evidence cannot still be drawn and larger prospective studies are needed, the exposure to low doses of environmental endocrine-disrupting contaminants can be considered consistent with the development of thyroid cancer.

Concentration-QT analysis of the randomized, placebo- and moxifloxacin-controlled thorough QT study of umeclidinium monotherapy and umeclidinium/vilanterol combination in healthy subjects.

The long-acting muscarinic antagonist umeclidinium (UMEC) is approved as a once-daily monotherapy and in combination with the long-acting ß2 agonist vilanterol (VI) for chronic obstructive pulmonary disease. The objective of this analysis was to assess the relationship between observed plasma UMEC and/or VI concentrations and QT interval corrected using Fridericia's correction (QTcF). 103 subjects were enrolled and 86 (83 %) completed the study. Subjects were randomized to 4 of 5 repeat-dose treatments (days 1-10: n = 77 subjects received placebo, n = 76 UMEC 500 µg, n = 78 UMEC/VI 125/25 µg, or n = 76 UMEC/VI 500/100 µg; day 10: n = 74 oral tablet moxifloxacin 400 mg [positive control]). The concentration-QTcF interval relationship was examined using nonlinear mixed-effects methods. For UMEC, predicted QTcF interval prolongation (at observed geometric mean of maximum plasma concentrations) was -2.38 ms (90 % prediction interval [PI] -3.82, -0.85) with UMEC 500 µg and -0.50 ms (90 % PI -0.80, -0.18) and -2.01 ms (90 % PI -3.22, -0.72) with UMEC/VI 125/25 µg and 500/100 µg, respectively. For VI, estimates were 5.89 ms (90 % PI 4.89, 6.91) and 7.23 ms (90 % PI 5.88, 8.55) with UMEC/VI 125/25 µg and 500/100 µg, respectively. Combined additive mean effects were estimated for UMEC/VI 125/25 µg (5.39 ms [90 % PI 4.40, 6.47]) and 500/100 µg (5.22 ms [90 % PI 3.72, 6.80]). The model-predicted decrease with UMEC and increase with UMEC/VI combination in QTcF interval suggest that the QT effect is likely attributable to VI. These model-predicted results support those of previously-published traditional statistical analyses.

Population Pharmacokinetics of Inhaled Fluticasone Furoate and Vilanterol in Subjects with Chronic Obstructive Pulmonary Disease.

BACKGROUND AND OBJECTIVES: Previous pharmacokinetic studies of the inhaled corticosteroid, fluticasone furoate (FF), and the long-acting, beta2-receptor agonist, vilanterol (VI) have been performed in relatively small populations using non-compartmental pharmacokinetic methods and censored data (due to low drug exposure relative to assay sensitivity). This paper presents a population pharmacokinetic analysis, utilizing pooled concentration-time data from clinical studies in healthy subjects and from global trials in patients with chronic obstructive pulmonary disease (COPD). The objective of this analysis was to characterize the population pharmacokinetics of FF and VI following once-daily inhalation dosing of FF/VI or the individual components (FF and VI) and to identify significant covariates that impact systemic exposure to FF and VI in this population. METHODS: Population pharmacokinetic methods that maximize the likelihood of all data were developed to describe systemic exposure to FF and VI following once-daily FF/VI, FF, or VI, and to identify significant covariates that impact the pharmacokinetics. COPD patients (N = 1225 for the FF analysis and N = 1091 for the VI analysis; 94 and 93 % of total data, respectively) and healthy subjects contributed to the analysis. RESULTS: FF data were described by a two-compartment model with first-order absorption and elimination. The population grouping "race" was a significant covariate on inhaled clearance (CL/F). The area under the curve over 24 h (AUC0-24) for FF was higher for East Asian, Japanese, and South East Asian (average 23-30 %) and Asian Central, White Arabic, American Indian/Native Alaskan, and 'other' (10-26 %) subjects compared with White/Caucasians. VI pharmacokinetics were described by a three-compartment model with zero-order absorption and first-order elimination. Significant demographic covariates identified to affect pharmacokinetics of VI were age [on CL/F and central volume (V 1/F)], bodyweight (on CL/F), sex and smoking (on V 1/F). CONCLUSIONS: While significant effects of the covariates were observed in this study, the magnitude of these effects on systemic exposure is not large enough to warrant FF/VI dosage adjustment in patients with COPD.

The organochlorine pesticides residues in the invasive ductal breast cancer patients.

Investigation of organochlorine pesticides residues (important environmental contamination causing malignant transformation) in breast cancer patients is valuable to understanding their roles in breast cancer. 75 invasive ductal carcinoma (IDC) patients were enrolled with control of 79 benign breast diseases patients and control of 80 healthy women. Morning fasting blood specimens and adipose tissue specimens beside the primary lesion were detected with gas chromatograph. In blood specimens, both levels of ß-HCH and PCTA were higher in IDC than those in both controls (both p<0.05), and increasingly higher among the three IDC degrees. In adipose tissue specimens, all levels of ß-HCH, PCTA and pp'-DDE were higher in IDC than those in control (all p<0.05) and increasingly higher among three IDC degrees. The levels of ß-HCH, PCTA in both blood specimens and adipose tissue specimens were higher in estrogen receptor (ER) positive IDC than those in ER negative IDC (all p<0.05). The higher level of organochlorine pesticides residues in blood and adipose tissue specimens of IDC infers its association with IDC, but the details remains to reveal, and this study may helpful in this field.

Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials.

BACKGROUND: The short-term benefits of inhaled corticosteroids for patients with chronic obstructive pulmonary disease (COPD) are greater in patients with evidence of eosinophilic airway inflammation. We investigated whether blood eosinophil count is a useful biomarker of the long-term effect of the inhaled corticosteroid fluticasone furoate on exacerbation frequency. METHODS: We did a post-hoc analysis of data from two replicate, randomised, double-blind trials of 12 months' duration (Sept 25, 2009 to Oct 21, 2011 and Oct 17, 2011) in which once a day vilanterol 25 µg was compared with 25 µg vilanterol plus 50 µg, 100 µg, or 200 µg fluticasone furoate in patients with moderate-to-severe COPD and a history of one or more exacerbation in the previous year. We compared exacerbation rates according to two baseline eosinophil cell count strata (<2% and ≥2%), and according to four baseline percentage groupings. We also assessed lung function and incidence of pneumonia per strata in treatment groups. FINDINGS: We included 3177 patients in the analyses, with 2083 patients (66%) having an eosinophil count of 2% or higher at study entry. Across all doses of inhaled corticosteroids, fluticasone furoate and vilanterol reduced exacerbations by 29% compared with vilanterol alone (mean 0·91 vs 1·28 exacerbations per patient per year; p<0·0001) in patients with eosinophil counts of 2% or higher, and by 10% (0·79 vs 0·89; p=0·2827) in patients with eosinophil counts lower than 2%. Reductions in exacerbations with fluticasone furoate and vilanterol, compared with vilanterol alone, were 24% in patients with baseline eosinophil counts of ≥2-<4%, 32% for those with counts of 4-<6%, and 42% for those with eosinophil counts of ≥6%. In patients treated with vilanterol alone, exacerbation rates increased progressively with increasing eosinophil count percentage category. Improvement in trough forced expiratory volume in 1 s (FEV1) and the increased risk of pneumonia with fluticasone furoate and vilanterol compared with vilanterol alone were not associated with eosinophil count. INTERPRETATION: Blood eosinophil count is a promising biomarker of response to inhaled corticosteroids in patients with COPD. Blood eosinophil count could potentially be used to stratify patients for different exacerbation rate reduction strategies. FUNDING: GlaxoSmithKline (study ID 201595).

The pharmacodynamics, pharmacokinetics, safety and tolerability of inhaled fluticasone furoate and vilanterol administered alone or simultaneously as fluticasone furoate/vilanterol.

PURPOSE: To investigate the potential for systemic pharmacokinetic (PK) and pharmacodynamic (PD) interactions between inhaled fluticasone furoate (FF) and vilanterol (VI) when delivered simultaneously via the ELLIPTA™ dry powder inhaler (DPI). METHODS: Randomized, double-blind, placebo-controlled, crossover study. Healthy subjects (n = 16) received single doses of FF (800 mcg), VI (100 mcg), FF/VI (800/100 mcg), and placebo. Endpoints measured were systemic PD (FF: serum cortisol; VI: heart rate), FF and VI plasma PK (0-48 hours), pharyngometry, inhalation and breath hold profiles and safety assessments. RESULTS: Treatment differences [90% confidence interval (CI)] in weighted mean serum cortisol (0-24 hours) were 12.3% [4.4, 20.9] (FF/VI vs. FF) and for maximum heart rate (0-4 hours) were -1.2 bpm [-4.6, 2.1] (FF/VI vs. VI). When delivered simultaneously, FF and VI systemic exposures were slightly lower (<20%) versus delivery of either agent alone (although this was not a formal bioequivalence study). In vitro simulation of selected inhalation profiles and modeling supported the PK and PD findings. FF/VI, FF and VI were well tolerated with an AE incidence comparable to placebo. CONCLUSIONS: These results suggest there was a slight PK interaction and no PD interactions of concern between inhaled FF and VI when delivered simultaneously via the ELLIPTA DPI in healthy subjects.

Pigmentation of the oral mucosa by PCB poisoning in Yusho patients.

OBJECTIVES: Toxins, such as PCBs, dramatically affect patients even decades after exposure. Although 40 years have passed since the accidental poisoning with polychlorinated biphenyl (PCB) in Western Japan in 1968, high concentrations of PCBs are still detected in the serum of the "Yusho" (oil disease) patients. In this study, an epidemiological examination was carried out to reveal the prevalence of the oral pigmentation and blood concentrations of PCBs and polychlorinated quaterphenyl (PCQ) in Yusho victims. DESIGN: We performed a group examination of patients (Yusho victims) from 2004 to 2006, including 72 Yusho victims and 15 control subjects. The oral examination was performed by two oral and maxillofacial surgeons. The serum concentrations of PCB and PCQ were determined using gas chromatography; blood samples from Yusho victims were analyzed for PCB and PCQ by saponification in 1M NaOH ethanol solution, extraction with n-hexane column chromatography on silica gel, and then gas chromatography with electron capture detection. RESULTS: The mean Yusho victim's serum PCB and PCQ concentrations were 3.3ppb and 0.9ppb, respectively. In controls, these were 0.7ppb and 0ppb, respectively. Oral pigmentation was observed in 24 out of 72 Yusho patients. In controls, oral pigmentation was observed in one out of 15 persons. Oral pigmentation was most frequently observed in the buccal mucosa, followed by gingival mucosa. The blood concentration of PCB in Yusho patients with oral pigmentations was significantly higher than that in Yusho patients without oral pigmentation. CONCLUSION: These results indicated that PCB-related compounds may be responsible for the higher prevalence of oral pigmentation in Yusho victims, even though a long time has passed since the Yusho poisoning accident.

Effect of verapamil on systemic exposure and safety of umeclidinium and vilanterol: a randomized and open-label study.

BACKGROUND: The combination of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a selective long-acting ß2 agonist, is in development for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the pharmacokinetics, safety and tolerability, and pharmacodynamics of once-daily, inhaled UMEC and UMEC/VI when co-administered with oral verapamil, a moderate P-glycoprotein transporter and moderate cytochrome P450 3A4 (CYP3A4) inhibitor frequently used by patients with COPD and cardiovascular comorbidities. METHODS: Subjects were randomized to one of two 13-day treatment regimens: UMEC 500 µg or UMEC 500 µg/VI 25 µg. All subjects received a single tablet containing 240 mg verapamil on each of days 9-13. RESULTS: Repeat doses of UMEC and UMEC/VI in combination with and without verapamil were safe and well tolerated. There was no increase in systemic exposure of UMEC when administered in combination with VI compared to UMEC alone. UMEC maximum concentration was similar with or without verapamil; a moderate increase in UMEC area under the curve (approximately 1.4-fold) was observed with verapamil. Verapamil did not increase systemic exposure to VI following administration of the UMEC/VI combination. CONCLUSION: Administration of UMEC and UMEC/VI combination was well tolerated and did not show clinically relevant increases in systemic exposure for either drug. The UMEC/VI combination is unlikely to have a clinically meaningful drug-drug interaction with moderate P-glycoprotein transporter and CYP3A4 inhibitor drugs.

Blood/air distribution of volatile organic compounds (VOCs) in a nationally representative sample.

Volatile organic compounds (VOCs) in human blood are an effective biomarker of environmental exposure and are closely linked to health outcomes. Unlike VOC concentrations in air, which are routinely collected, blood VOC data are not as readily available. This study aims to develop the quantitative relationship between air and blood VOCs by deriving population-based blood/air distribution coefficients (popKs) of ten common VOCs in the general U.S. population. Air and human blood samples were collected from 364 adults aged 20-59 years in 1999-2000 National Health and Nutrition Examination Survey (NHANES). Determinants of popKs were identified using weighted multivariate regression models. In the non-smoking population, median popKs ranged from 3.1 to 77.3, comparable to values obtained in the laboratory. PopKs decreased with increasing airborne VOC concentrations. Smoking elevated popKs by 1.5-3.5 times for aromatic compounds, but did not affect the popKs for methyl tert-butyl ether (MTBE) or chlorinated compounds. Drinking water concentration was a modifier of MTBE's popK. Age, gender, body composition, nor ethnicity affected popKs. PopKs were predictable using linear models with air concentration as the independent variable for both adults and children. This is the first study to estimate blood/air distribution coefficients using simultaneous environmental and biological monitoring on a national population sample. This study was also the first to determine the blood/air distribution coefficient of p-dichlorobenzene, a compound frequently found in indoor environments. These results have applications in exposure assessment, pharmacokinetic analysis, physiologically-based pharmacokinetic (PBPK) modeling, and uncertainty analysis.

[The rapid analysis of polychlorinated quaterphenyls in blood using different diameter capillary column with the high-resolution gas chromatograph high-resolution mass spectrometer].

The polychlorinated quaterphenyl (PCQ) concentrations in blood are important discriminative parameters in yusho patient. In this study, a rapid analytical method for PCQ using different diameter capillary column (rapid-Rtx65TG) with high-resolution gas chromatograph high-resolution mass spectrometer (HRGC/HRMS) instead of the gas chromatograph electron capture detector (ECD/GC) was developed. Using different diameter capillary columns, the analysis time of the HRGC/HRMS was drastically shortened, and the detection sensitivity was improved. In the rapid-Rtx65TG column, a small-bore capillary column (length 1m, I.D. 0.1mm) was connected with the inlet side of the GC, and behind that column, a large-bore capillary column (length 15mm, I.D. 0.53mm) for octadecachloroquaterphenyl (ODCQ) analysis was connected. In the HRGC/HRMS measurement of ODCQ by the rapid-Rtx65TG column, the minimum limit of detection for the apparatus was 0.4 pg, and the minimum limit of determination for the blood was 0.008 ppb. On ECD/GC in the conventional method and HRGC/HRMS in this study, the PCQ concentration in blood including yusho patients and yusho suspected persons was almost equivalent.

Concentrations of selected organochlorines and chlorobenzenes in the serum of former Love Canal residents, Niagara Falls, New York.

BACKGROUND: Love Canal, in Niagara Falls, NY is among the earliest and most significant hazardous waste sites in the USA, but no study has ever measured chemical body burdens in nearby residents to document that human exposure occurred. This study measured concentrations of selected organochlorines and chlorinated benzenes in archived serum samples collected from former Love Canal residents. METHODS: We analyzed serum samples collected from 373 former residents in 1978-1979 for compounds disposed of at Love Canal, and we compared their concentrations according to surrogate indicators of exposure such as residential proximity, adjusting for potential confounders. RESULTS: Three compounds were detectable in the serum of most participants: 1,2,4-trichlorobenzene (1,2,4-TCB), beta-hexachlorocyclohexane (beta-HCH) and 1,2-dichlorobenzene (1,2-DCB). Concentrations of 1,2,4-TCB and 1,2-DCB were 2-14 times greater among persons who at the time their blood was collected lived closest to the Canal compared to those living further away. We found no consistent trends for beta-HCH with respect to any exposure definition. CONCLUSIONS: These results provide evidence that residential proximity to Love Canal contributed to the body burden of certain contaminants, and helps validate the use of surrogate exposure measures in health effect studies. Further surveillance of the Love Canal cohort is warranted.

Simple isotope dilution headspace-GC-MS analysis of naphthalene and p-dichlorobenzene in whole blood and urine.

A very simple and sensitive method for the simultaneous analysis of naphthalene and p-dichlorobenzene in human whole blood and urine by headspace capillary gas chromatography-mass spectrometry (GC-MS) is presented. The advantages of the method were that as much as 1 mL of headspace vapor could be injected into a GC port in the splitless mode, and that the addition of deuterated naphthalene and p-dichlorobenzene as internal standards resulted in much better headspace extraction efficiencies, which resulted in high sensitivity. The detection limits for both naphthalene and p-dichlorobenzene were 1 ng mL(-1) for whole blood and 0.5 ng mL(-1) for urine. Validation data, such as the linearity of calibration curves, reproducibility and recovery rates, were all satisfactory. Using this method, both compounds could actually be detected from whole blood samples of a male volunteer after the inhalation of each gas of the compounds.

[Bone mineral density, PCB, PCQ and PCDF in Yusho].

We measured bone mineral density of the distal end of radius with dual energy X-ray absorptiometry, serum cross-linked N-telopeptides of type I collagen, serum bone-specific alkaline phosphatase, serum Ca, serum P, blood PCB level, blood PCQ level and blood PCDF level in Yusho. As a result, the osteoporosis group (< 70% of the young adult mean [YAM] bone mineral density [BMD]) was observed in 7.1% of the studied male subjects. And, the moderate group (> or = 70% and < 80% of YAM BMD), 16.1%, the normal (> or = 80% of YAM BMD) group was 76.8%. Also, 42.3% of all female tested subjects observed in osteoporosis group. The moderate group, 19.2%, the normal group was 38.5%. There was no difference in PCB blood level, PCQ, PCDF for men and women in osteoporosis group, moderate group, and in the normal group. Serum cross-linked N-telopeptides of type I collagen increased in the male osteoporosis group, but serum bone-specific alkaline phosphatase did not change. This study was inconclusive since the results did not determine the influence that PCB, PCQ, PCDF gave to bone density and bone metabolism.

Pentachlorobenzene, hexachlorobenzene, and pentachlorophenol in children's serum from industrial and rural populations after restricted use.

The study of a population of 4-year-old children born between 1997 and 1999 in an urban area under strong inputs of pentachlorobenzene (PeCB) and hexachlorobenzene (HCB) suggested that the measured concentrations of pentachlorophenol (PCP) in serum may essentially result from metabolism of these chlorinated hydrocarbons. In contrast, examination of a rural population of children where the same compounds were present at relatively low levels points to other inputs besides transformation of PeCB and HCB being responsible for the measured PCP concentrations. In both populations, the results showed that a major proportion of the organochlorine compounds present in these children's serum at 4 years of age was incorporated during the lactation period.