Exposure to environmental phenols and parabens, and relation to body mass index, eczema and respiratory outcomes in the Norwegian RHINESSA study.

BACKGROUND: Many phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index. METHODS: Demographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10-17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry. RESULTS: Detection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant. CONCLUSIONS: Reported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.

Methyl Paraben May Increase Risk of Pruritus in African Americans Whereas Triclosan Is Inversely Associated With Pruritus and Eczema.

BACKGROUND: Phenols and parabens (P&Ps) are commonly found in skin care products. However, P&Ps' role in pruritus and eczema has not been studied. OBJECTIVE: The aim of the study was to investigate the association between P&Ps, and pruritus and eczema. METHODS: This is a cross-sectional population-based study of 2202 participants. We examined the association between urinary phenols (triclosan, bisphenol A, benzophenone-3) and parabens (methyl and propyl parabens) and itchy rash/eczema using the 2005-2006 National Health and Nutrition Examination Survey database. Phenols and parabens were divided into quartiles (Qs) with the first Q as the reference. We calculated odds ratios and 95% confidence intervals, adjusting for multiple variables. RESULTS: Urinary triclosan was inversely associated with itchy rash (P trend = 0.048). In a subpopulation analysis by race/ethnicity, urinary methyl paraben was positively associated with itchy rash in African Americans (fourth Q vs first Q: odds ratio, 12.60; 95% confidence interval, 1.03-154.06; P trend = 0.02). Triclosan was inversely associated with eczema in whites (P trend = 0.04). CONCLUSIONS: Methyl paraben exposure may increase the risk of itchy rash in African Americans, whereas triclosan may decrease the risk of itchy rash and eczema. The potential effect of triclosan and methyl paraben in pruritus and eczema warrants further study.

Multiple exposures to organophosphate flame retardants alter urinary oxidative stress biomarkers among children: The Hokkaido Study.

Organophosphate flame retardants (PFRs) are used as additives in plastics and other applications such as curtains and carpets as a replacement for brominated flame retardants. As such, exposure to PFR mixtures is widespread, with children being more vulnerable than adults to associated health risks such as allergies and inflammation. Oxidative stress is thought to be able to modulate the development of childhood airway inflammation and atopic dermatitis. To evaluate these associations, the present study investigated the relationship between urinary PFR metabolites, their mixtures and urinary oxidative stress biomarkers in children as part of the Hokkaido Study on Environment and Children's Health. The levels of the oxidative stress biomarkers, such as 8-hydroxy-2'-deoxyguanosine (8-OHdG), hexanoyl-lysine (HEL), and 4-hydroxynonenal (HNE), and of 14 PFR metabolites were measured in morning spot urine samples of 7-year-old children (n = 400). Associations between PFR metabolites or PFR metabolite mixtures and oxidative stress biomarkers were examined by multiple regression analysis and weighted quantile sum regression analysis, respectively. We found that the non-chlorinated PFR metabolites, 2-ethylhexyl phenyl phosphate (EHPHP), bis(2-butoxyethyl) phosphate (BBOEP), and diphenyl phosphate (DPHP) were associated with increased levels of oxidative stress biomarkers. Furthermore, the PFR metabolite mixture was associated with increased levels of HEL and HNE, but not 8-OHdG. The combination of elevated top 2 PFR metabolites was not associated with higher urinary oxidative stress marker levels. This is the first study to report associations between urinary PFR metabolites and oxidative stress biomarkers among children.

Urinary phthalate metabolites in relation to childhood asthmatic and allergic symptoms in Shanghai.

BACKGROUND: Few studies can be found on phthalate exposure in relation to childhood asthma and allergic symptoms from Mainland China, where a persistent increase in prevalence of childhood asthma and allergic disease has been observed. OBJECTIVES: This study aimed to assess the exposure levels to phthalates and its relationship with asthmatic and allergic symptoms among children in Shanghai, which has the highest prevalence of childhood asthma in Mainland China. METHODS: A follow-up study (2013-2014) of 434 children aged 5-10 years was conducted, based on the China, Children, Homes, Health (CCHH) study (2011-2012) in Shanghai, China. Information on asthmatic and allergic symptoms (wheeze, rhinitis, and eczema) were collected using validated questionnaires. Ten phthalate metabolites in morning urine samples were analyzed by high-performance liquid chromatography with triple quadrupole tandem mass spectrometry (HPLC-MS/MS). Multivariable logistic regression was used to estimate the associations between symptoms and urinary phthalate metabolites controlling for demographics, family history of allergic diseases and other covariates. RESULTS: Nine out of 10 phthalate metabolites were detected in all subjects (average detection rate of 93.2%). By multivariable logistic regression analyses, the 4th quartile of Mono­n­butyl phthalate (MnBP) (reference: 1st quartile) had adjusted prevalence odds ratios (aPORS) and 95% confidence intervals (95%CIs) of 2.27(1.06-4.88), 2.14(1.02-4.46) and 2.98(1.19-7.50) for wheeze, rhinitis and eczema, respectively, while those of Mono­isobutyl phthalate (MiBP) were 2.23(1.08-4.62) and 2.96(1.02-8.60) for rhinitis and eczema, respectively. The highest quartile of mono­2­ethyl­5­hydroxyhexyl phthalate(MEHHP) and mono­2­ethyl­5­oxohexyl phthalate(MEOHP) had aPORS and 95%CIs of 3.10(1.10-8.74) and 2.63(1.02-6.80) for eczema, respectively. By summing up the 4 low molecular weight metabolites (∑4LMWP) and all 9 metabolites (∑9Total), the highest quartiles of ∑4LMWP and∑9Total were significantly associated with all symptoms. In most of the above associations, a significantly increasing trend from the 1st to the 4th quartile was observed. Subjects with 2 or 3 concomitant symptoms (reference: no symptoms) had significant positive associations with a higher level (the 4th quartile) of phthalate metabolites. CONCLUSIONS: Low MW metabolites such as MnBP and MiBP, high MW DEHP and the total amount of phthalate metabolites might have adverse health effects on asthma and allergic symptoms in Chinese children.

Associations between allergic symptoms and phosphate flame retardants in dust and their urinary metabolites among school children.

BACKGROUND: Phosphate flame retardants (PFRs) are ubiquitously detected in indoor environments. Despite increasing health concerns pertaining to PFR exposure, few epidemiological studies have examined PFR exposure and its effect on children's allergies. OBJECTIVES: To investigate the association between PFRs in house dust, their metabolites in urine, and symptoms of wheeze and allergies among school-aged children. METHODS: A total of 128 elementary school-aged children were enrolled. House dust samples were collected from upper-surface objects. Urine samples were collected from the first morning void. Levels of 11 PFRs in dust and 14 PFR metabolites in urine were measured. Parent-reported symptoms of wheeze, rhinoconjunctivitis, and eczema were evaluated using the International Study of Asthma and Allergies in Childhood questionnaire. The odds ratios (ORs) of the Ln transformed PFR concentrations and categorical values were calculated using a logistic regression model adjusted for sex, grade, dampness index, annual house income, and creatinine level (for PFR metabolites only). RESULTS: The prevalence rates of wheeze, rhinoconjunctivitis, and eczema were 22.7%, 36.7%, and 28.1%, respectively. A significant association between tris(1,3-dichloroisopropyl) phosphate (TDCIPP) in dust and eczema was observed: OR (95% confidence interval), 1.44 (1.13-1.82) (>limit of detection (LOD) vs LOD vs

IgE antibodies and urinary trimethylarsine oxide accounted for 1-7% population attributable risks for eczema in adults: USA NHANES 2005-2006.

Population attributable risks from serum IgE and dust miteallergen concentrations and environmental chemicals for eczema are unclear. Therefore, it was aimed to examine serum IgE and allergen concentrations and environmental chemicals for eczema in adults and to calculate population attributable risks in a national and population-based setting. Data retrieved from the National Health and Nutrition Examination Survey, 2005-2006, was analyzed. Information on demographics and self-reported ever eczema was obtained by household interview. Bloods and urines (sub-sample) were also collected during the interview. Adults aged 20-85 were included. Statistical analyses were using chi-square test, t test, survey-weighted logistic regression modeling, and population attributable risk (PAR) estimation. Of all the included American adults (n = 4979), 310 (6.2%) reported ever eczema. Moreover, more eczema cases were observed in female adults but fewer cases in people born in Mexico. There were no significant associations observed between commonly known biomarkers (including vitamin D) and eczema or between dust mite allergens and eczema. Serum D. Farinae (PAR 1.0%), D. Pteronyssinus (PAR 1.1%), cat (PAR 1.8%), dog (PAR 1.6%), and muse (PAR 3.2%) IgE antibodies were associated with eczema. Adults with ever eczema were found to have higher levels of urinary trimethylarsine oxide concentrations (PAR 7.0%) but not other speciated arsenic concentrations. There were no clear associations between other environmental chemicals including heavy metals, phthalates, phenols, parabens, pesticides, nitrate, perchlorate, polycyclic hydrocarbons and eczema as well. Elimination of environmental risks might help delay or stop eczema up to 7% in the adult population.

The effect of prenatal exposure to phthalates on food allergy and early eczema in inner-city children.

BACKGROUND AND OBJECTIVE: We hypothesized that maternal prenatal and children urine metabolite concentration of phthalates would be associated with food allergy and early eczema among inner-city children. The study was based on data from the Polish Mother and Child Cohort. METHODS: Prenatal and postnatal exposure to the following phthalates: diethyl phthalate, diisobutyl phthalate, di-n-butyl phthalate, butyl-benzyl phthalate, di(2-ethylhexyl) phthalate, diisononyl phthalate, and di-n-octyl phthalate were determined by measuring phthalate metabolites in the urine collected from the mothers during the third trimester of pregnancy and from their children at age 2 years. Pre- and postnatal observations limited the response rate and final sample size; data from 147 participants were included in the analysis. Children's health status was assessed at 24 months of age by using a questionnaire administered to the mothers. We studied associations between the urine level of phthalates and the presence of food allergy and atopic dermatitis in logistic regression analysis. All associations were adjusted for independent risk factors of dependent variables. Associations with atopic dermatitis were adjusted for the effect of atopy in the family, the father's education, frequency of house cleaning, and breastfeeding; associations with food allergy were adjusted for the presence of pets at home during pregnancy and breastfeeding. RESULTS: The prevalence of the outcomes were as follows: atopic dermatitis, 12.2%, and food allergy, 48.9%. We showed that higher urine concentrations of monobenzyl phthalate in mothers during pregnancy increased the risk of food allergy in children during the first 2 years of life (odds ratio 4.17 [95% confidence interval, 1.17-17.89]). There were no associations with children's urine and allergic symptoms. CONCLUSIONS: Results of our study indicated awareness of environmental factors that may affect children's health because the phthalates were shown to be risk factors for food allergy in children.

Exposure to ambient ultrafine particles and urinary 8-hydroxyl-2-deoxyguanosine in children with and without eczema.

Ambient fine and ultrafine particles (UFPs) in urban air are known to contribute to inflammatory and allergic disease. It has been suggested that oxidative stress is an underlying mechanism for the detrimental health effects. The objective of this study was to investigate the short-term effect of ambient UFPs and particulate polycyclic aromatic hydrocarbons (PAHs) on urinary 8-hydroxyl-2-deoxyguanosine (8-OHdG) concentrations in children with and without eczema. Spot urine samples were collected from 84 children twice weekly for 61 days and 8-OHdG content was measured. Significant associations were found between the ambient UFPs and particle bound PAHs and increase in urinary 8-OHdG levels. An inter-quartile range (IQR) increase in the UFP concentration in the 24-h (IQR, 32,300/m(3)) period preceding urine collection was significantly associated with a 5.7% (95% confidence interval [CI], 0.16-1.27%) increase in the urinary 8-OHdG level children with AD. In children without eczema, such short-term effect of previous day UFPs on urinary 8-OHdG was not observed. There were no significant positive associations between the mass fraction of PMs and urinary 8-OHdG. The results suggest that short-term exposure to ambient UFPs plays a critical role in PM induced oxidative stress in children with eczema.

Percutaneous penetration via hand eczema is the major accelerating factor for systemic absorption of toluene and xylene during car spray painting.

BACKGROUND: For absorption of organic solvents, the respiratory tract is well known as the major site, but percutaneous absorption might be critical in some workplaces. OBJECTIVES: The aim of the study is to determine whether the skin, if disordered, is 1 of the major routes of organic solvent absorption. PATIENTS/METHODS: 72 male workers who painted the car body in the booth of a Japanese car company were participated in this study. The severity of hand eczema, urinary metabolites of organic solvents and the concentration of airborne organic solvents were measured. RESULTS: The correlation coefficiency between the skin severity index and the urinary concentration of hippuric acid or methylhippuric acid was statistically significant. There was no significant correlation between their urinary values and the air concentration of mixed organic solvents. CONCLUSIONS: The skin is a more critical absorption route for organic solvents than the respiratory tract in some occupational settings. Hand eczema is a common disease and has a possibility to be a critical absorption route of organic solvents.

Urinary eosinophilic protein X, atopy, and symptoms suggestive of allergic disease at 3 years of age.

BACKGROUND: Urinary eosinophilic protein X (U-EPX) measurement is easy to perform in children. However, its use for prediction, diagnosis, and monitoring of asthma and atopy is unclear. OBJECTIVE: We sought to investigate the relationship between U-EPX and clinical phenotypes suggestive of allergic diseases. METHODS: U-EPX measurement (RIA), respiratory questionnaires, and skin testing were completed at age 3 years in 903 children followed prospectively from birth. Specific airway resistance was measured in 503 currently asymptomatic children by using whole-body plethysmography during tidal breathing. RESULTS: Nonatopic children with wheezing or eczema had slightly increased U-EPX levels compared with nonatopic asymptomatic children. U-EPX levels (geometric mean EPX/creatinine ratio) were as follows: nonatopic asymptomatic children (n = 313), 61.3 microg/mmol (95% CI, 56.4-66.6 microg/mmol); nonatopic children with wheezing (n = 148), 71.2 microg/mmol (95% CI, 63.2-80.1 microg/mmol); nonatopic children with eczema (n = 90), 65.7 microg/mmol (95% CI, 56.7-76.2 microg/mmol); and nonatopic children with wheezing and eczema (n= 86), 79.7 microg/mmol (95% CI, 67.4-94.3 microg/mmol). Children who had persistent atopy early in life had significantly higher U-EPX levels at age 3 years (nonatopic at 1 and 3 years [n = 263], 63.4 microg/mmol [95% CI, 58.4-69.0 microg/mmol]; atopic at 1 but not 3 years [n = 24], 65.1 microg/mmol [95% CI, 43.8-96.7 microg/mmol]; nonatopic at 1 year and atopic at 3 years [n = 62], 90.0 microg/mmol [95% CI, 74.6-108.4 microg/mmol]; atopic at 1 and 3 years [n = 35], 111.5 microg/mmol [95% CI, 89.2-139.3 microg/mmol]; P <.002). Atopy alone and with wheezing, eczema, or both was associated with significantly increased U-EPX levels (P <.0001). Wheezing appeared to be associated with higher U-EPX levels compared with eczema in both atopic and nonatopic children. The highest U-EPX level was found in atopic children with a history of wheezing and eczema (P <.0001). There was no relationship between U-EPX level and lung function. CONCLUSION: U-EPX level reflects the presence of atopy and associated symptoms and might be useful for monitoring the progression of allergic disease.

Urinary leukotriene levels are increased during exacerbation of atopic eczema/dermatitis syndrome. Relation to clinical status.

BACKGROUND: Leukotrienes are potent mediators of allergic inflammation and their role in the pathogenesis of allergic disorders, particularly asthma, is well established. Their importance in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS) is still unclear. We aimed to compare urinary cysteinyl leukotriene (Cys-LT) levels during exacerbation and remission of AEDS in relation to clinical status, IgE levels, and eosinophil counts. METHODS: Urinary Cys-LTs were measured by direct enzyme immunoassay in 17 adult patients with AEDS and in 17 healthy controls in whom atopy had been excluded. Cys-LTs were compared during exacerbation and remission of AEDS in relation to the clinical status measured by SCORAD. Total IgE levels were measured by enzyme-linked immunoassay (ELISA). RESULTS: Mean clinical score during the exacerbation was 64.3 +/- 3.1 and during remission 22.4 +/- 4 (P < 0.01). Cys-LTs levels were significantly higher during the exacerbation of AEDS than in the control group (230.9 +/- 20.8 vs 123.2 +/- 9.9 pg/mg creatinine; P < 0.005). During the remission, the difference between AEDS patients and the control group was not significant (96.3 +/- 8.7 vs 123.2 +/- 9.9 pg/mg creatinine; P = 0.8). During AEDS exacerbation Cys-LTs levels were significantly correlated with the clinical status (rS = 0.73, P < 0.01) and with eosinophil counts (r = 0.86; P < 0.01) but not with the duration of the disease, age of patients, or IgE levels. CONCLUSIONS: Our results point to enhanced biosynthesis of Cys-LTs during the AEDS exacerbations. Inflammatory cells, e.g. eosinophils are the most probable source of Cys-LTs. A strong correlation between Cys-LT levels and clinical status may in part explain preliminary clinical observations of efficacy of leukotriene antagonists in alleviating symptoms of AEDS.

[Disorders of steroid metabolism in inflammatory skin diseases]. / Störung des Steroidmetabolismus bei entzündlichen Hauterkrankungen.

The corticosteroid and androgen metabolites in the urine of 37 test subjects (11 healthy volunteers, 16 patients with eczema, and 10 patients with psoriasis) were investigated by means of gas chromatography and mass spectrometry. In addition, we studied the cortisol and testosterone levels in the plasma by radioimmunoassay. Those patients who had been treated with corticosteroids during the last two weeks were excluded. Our findings revealed that the excretion rate of steroid metabolites was significantly reduced in dermatological patients. The excretion rate of corticosteroids in urine was decreased an average of 25% (eczema) and 29% (psoriasis). The reduction of the androgen metabolites amounted to 26% and 31%. Cortisol and testosterone levels in the plasma were normal in all the cases.

Histamine metabolism in patients with histidinemia: determination of urinary levels of histamine, N tau-methylhistamine, imidazole acetic acid, and its conjugate(s).

Histamine metabolism in histidinemic patients was studied by measuring the urinary levels of histamine and its metabolites. The urinary excretions of histamine, N tau-methylhistamine, imidazole acetic acid, and its conjugate(s) were higher in patients with histidinemia than in controls, and these levels of excretion were correlated with the plasma histidine level. The urinary histamine levels of patients with eczema-like dermatitis were twice that of those without dermatitis. The urinary excretion of 3-methylhistidine showed a close correlation with the urinary histidine excretion. Thus, it was concluded that histamine metabolism is higher in histidinemic patients than in normal controls.

Factors influencing nickel dermatitis. I.

The nickel concentrations in urine and blood plasma of a very hypersensitive female patient have been followed during two periods of 34 and 42 days each. A limited degree of correlation was found between the course of the nickel concentration in plasma, the nickel concentration in urine and the clinical activity of the dermatitis. Evidently other factors also influence the activity of the dermatitis; among these menstruation and stress might be expected to play a role.

Factors influencing nickel dermatitis. II.

The nickel concentrations in urine and other data of a very hypersensitive female patient have been followed during two periods exceeding 30 days each. Only a limited degree of correlation was found between the course of the nickel concentration in urine and the clinical activity of the dermatitis. In order to better evaluate the measure of the correlation and the influence of some other factors upon the activity of the dermatitis, a pathway analysis scheme has been constructed. Consideration of this scheme reveals the need for more extensive data regarding the nickel ion climate in the body.