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1.
Food Chem Toxicol ; 81: 71-80, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25846501

RESUMO

Systemic exposure was measured in humans after hair dyeing with oxidative hair dyes containing 2.0% (A) or 1.0% (B) [(14)C]-p-phenylenediamine (PPD). Hair was dyed, rinsed, dried, clipped and shaved; blood and urine samples were collected for 48 hours after application. [(14)C] was measured in all materials, rinsing water, hair, plasma, urine and skin strips. Plasma and urine were also analysed by HLPC/MS/MS for PPD and its metabolites (B). Total mean recovery of radioactivity was 94.30% (A) or 96.21% (B). Mean plasma Cmax values were 132.6 or 97.4 ng [(14)C]-PPDeq/mL, mean AUC(0-∞) values 1415 or 966 ng [(14)C]-PPDeq/mL*hr in studies A or B, respectively. Urinary excretion of [(14)C] mainly occurred within 24 hrs after hair colouring with a total excretion of 0.72 or 0.88% of applied radioactivity in studies A or B, respectively. Only N,N'-diacetylated-PPD was detected in plasma and the urine. A TK-based human safety assessment estimated margins of safety of 23.3- or 65-fold relative to respective plasma AUC or Cmax values in rats at the NOAEL of a toxicity study. Overall, hair dyes containing PPD are unlikely to pose a health risk since they are used intermittently and systemic exposure is limited to the detoxified metabolite N,N'-diacetyl-PPD.


Assuntos
Tinturas para Cabelo/química , Fenilenodiaminas/farmacocinética , Adulto , Área Sob a Curva , Isótopos de Carbono , Cromatografia Líquida de Alta Pressão , Qualidade de Produtos para o Consumidor , Feminino , Cabelo/química , Cabelo/efeitos dos fármacos , Humanos , Masculino , Nível de Efeito Adverso não Observado , Fenilenodiaminas/sangue , Fenilenodiaminas/urina , Espectrometria de Massas em Tandem , Adulto Jovem
2.
Regul Toxicol Pharmacol ; 63(1): 171-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22406137

RESUMO

We measured consumer exposure to formaldehyde (FA) from personal care products (PCP) containing FA-releasing preservatives. Six study subjects applied facial moisturiser, foundation, shower gel, shampoo, deodorant, hair conditioner, hair styling gel or body lotion at the 90th percentile amount of EU PCP consumer use. FA air concentrations were measured in the empty room, in the presence of study subjects prior to PCP use, and for one hour (breathing zone, area monitoring) after PCP use. The mean FA air concentration in the empty bathroom was 1.32 ± 0.67 µg/m³, in the presence of subjects it was 2.33 ± 0.86 µg/m³). Except for body lotion and hair conditioner (6.2 ± 0.1.9 or 4.5 ± 0.1.5 µg/m³, respectively), mean 1-h FA air concentrations after PCP use were similar to background. Peak FA air concentrations, ranging from baseline values (2.2 µg/m³; shower gel) to 11.5 µg/m³ (body lotion), occurred during 0-5 to 5-10 min after PCP use. Despite of exaggerated exposure conditions, FA air levels were a fraction of those considered to be safe (120 µg/m³), occurring in indoor air (22-124 µg/m³) or expired human breath (1.4-87 µg/m³). Overall, our data yielded evidence that inhalation of FA from the use of PCP containing FA-releasers poses no risk to human health.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Cosméticos/análise , Formaldeído/análise , Exposição por Inalação/análise , Adulto , Qualidade de Produtos para o Consumidor , Monitoramento Ambiental , Feminino , Humanos , Medição de Risco , Adulto Jovem
3.
Public Health Nutr ; 14(3): 410-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20707949

RESUMO

OBJECTIVE: To validate an FFQ designed to estimate energy intake in children against doubly labelled water (DLW). To investigate how quality control and standard beverage portion sizes affect the validity of the FFQ. DESIGN: Thirty healthy children, aged 4-6 years, participated. Total energy expenditure (EE) was measured by the DLW method during an observation period of 15 d. At the end of this period parents filled out an FFQ designed to assess the child's habitual energy intake (EI) of the preceding four weeks. SETTING: Validation study in The Netherlands. SUBJECTS: Thirty healthy children (fifteen boys and fifteen girls), aged 4-6 years. RESULTS: Mean EI (6117 (sd 1025) kJ/d) did not differ significantly from mean EE (6286 (sd 971) kJ/d; P = 0·15); the mean EI:EE ratio was 0·98. The Pearson correlation coefficient between EI and EE was 0·62. The Bland-Altman plot showed no systematic bias and a constant bias close to zero. Less intensive quality control of the FFQ maintained the mean EI:EE ratio and decreased the correlation slightly. Using standard instead of individually measured beverage portion sizes decreased the mean EI:EE ratio, but maintained the correlation. CONCLUSIONS: It can be concluded that the developed FFQ is a valid instrument to estimate mean energy intake in a group of 4- to 6-year-old children and performs reasonably well to rank the subjects with respect to energy intake. It is therefore a useful instrument to estimate energy intake in children in surveys and epidemiological studies in The Netherlands.


Assuntos
Bases de Dados Factuais , Ingestão de Energia , Inquéritos e Questionários , Antropometria , Criança , Pré-Escolar , Deutério , Registros de Dieta , Inquéritos sobre Dietas , Metabolismo Energético , Feminino , Humanos , Masculino , Países Baixos , Isótopos de Oxigênio/análise , Controle de Qualidade , Análise de Regressão
4.
Clin Pharmacokinet ; 46(10): 851-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17854234

RESUMO

BACKGROUND AND OBJECTIVE: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch containing radiolabelled [(14)C]rotigotine and to quantify the pharmacokinetic profiles of total radioactivity and the corresponding rotigotine plasma concentrations. METHODS: In a phase I trial, six healthy male Caucasian subjects were administered a single 10 cm(2) patch containing 4.485mg of unlabelled and 0.015mg of [(14)C]-labelled rotigotine (total radioactivity 0.09 MBq per patch) with a patch-on period of 24 hours. Radioactivity was determined by liquid scintillation counting in unused patches, used patches, skin wash samples after 24 hours, plasma, urine and faeces samples up to 96 hours and skin stripping samples at 96 hours post-application. Unconjugated rotigotine in plasma samples was determined by liquid chromatography with tandem mass spectrometry. Plasma samples were taken predose and 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours after patch application. RESULTS: The rotigotine transdermal patch was well tolerated, and all subjects completed the trial. A total of 94.6% of the administered dose was recovered within 96 hours after patch application inclusive of the residual amounts in the patch. Within 24 hours, 51% of the total radioactivity was delivered to the human body system and 46.1% was systemically absorbed. Total radioactivity recovered in urine and faeces was 30.4% and 10.2%, respectively, of the radioactivity applied (corresponding to 65.8% and 21.8% of the dose absorbed, respectively). CONCLUSIONS: The mass balance of rotigotine within 96 hours after transdermal delivery of rotigotine via a 10 cm(2) [(14)C]rotigotine patch with a total drug content of 4.5mg (corresponding to the nominal dose of 2mg/24 hours for the marketed rotigotine transdermal system) has been 95% explained. The systemic absorption was 46.1% of the administered dose, the majority of which was cleared from the body via urine and faeces within 96 hours after patch application.


Assuntos
Agonistas de Dopamina/administração & dosagem , Tetra-Hidronaftalenos/administração & dosagem , Tiofenos/administração & dosagem , Administração Cutânea , Adolescente , Adulto , Radioisótopos de Carbono , Cromatografia Líquida , Agonistas de Dopamina/sangue , Agonistas de Dopamina/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Tetra-Hidronaftalenos/sangue , Tetra-Hidronaftalenos/farmacocinética , Tiofenos/sangue , Tiofenos/farmacocinética
5.
Food Chem Toxicol ; 45(1): 160-9, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17030383

RESUMO

We monitored the exposure of hairdressers to oxidative hair dyes for 6 working days under controlled conditions. Eighteen professional hairdressers (3/day) coloured hairdresser's training heads bearing natural human hair (hair length: approximately 30 cm) for 6 h/working day with a dark-shade oxidative hair dye containing 2% [14C]-para-phenylenediamine (PPD). Three separate phases of hair dyeing were monitored: (A) dye preparation/hair dyeing, (B) rinsing/shampooing/conditioning and (C) cutting/drying/styling. Ambient air and personal monitoring samples (vapours and particles), nasal and hand rinses were collected during all study phases. Urine (pre-exposure, quantitative samples for the 0-12, 12-24, 24-48 h periods after start of exposure) and blood samples (blank, 4, 8 or 24 h) were collected from all exposed subjects. Radioactivity was determined in all biological samples and study materials, tools and washing liquids, and a [14C]-mass balance was performed daily. No adverse events were noted during the study. Waste, equipment, gloves and coveralls contained 0.41+/-0.16%, dye mixing bowls 2.88+/-0.54%, hair wash 45.47+/-2.95%, hair+scalp 53.46+/-4.06% of the applied radioactivity, respectively. Plasma levels were below the limit of quantification (10 ng PPDeq/mL). Total urinary 0-48 h excretion of [14C] levels ranged from a total of <2-18 microg PPDeq and was similar in subjects exposed during the different phases of hair dyeing. Minimal air levels at or slightly above the limit of quantification were found in a few personal air monitoring samples during the phases of hair dyeing and hair cutting, but not during the rinsing phase. Air area monitoring samples or nasal rinses contained no measurable radioactivity. Hand residues ranged from 0.006 to 0.15 microg PPDeq/cm2, and were found predominantly after the cutting/drying phase. The mean mass balance of [14C] across the six study days was 102.50+/-2.20%. Overall, the mean, total systemic exposure of hairdressers to oxidative hair dyes during a working day including 6 hair dyeing processes was estimated to be <0.36 microg PPDeq/kg body weight/working day. Our results suggest that (a) current safety precautions for the handling of hair dyes offer sufficient protection against local and systemic exposure and (b) professional exposure to oxidative hair dyes does not pose a risk to human health.


Assuntos
Indústria da Beleza , Monitoramento Ambiental/métodos , Tinturas para Cabelo/farmacocinética , Exposição Ocupacional/análise , Fenilenodiaminas/farmacocinética , Adulto , Radioisótopos de Carbono , Feminino , Luvas Protetoras , Tinturas para Cabelo/análise , Desinfecção das Mãos , Humanos , Masculino , Pessoa de Meia-Idade , Fenilenodiaminas/análise
6.
Int Arch Occup Environ Health ; 78(1): 44-50, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15627216

RESUMO

OBJECTIVE: The methods and results are described of a study on the dermal absorption of chlorpyrifos (CPF) in humans established via urinary excretion of the metabolite 3,5,6-trichloro-2-pyridinol (TCP). METHODS: Two dermal, single, doses of CPF were applied in two study groups (A and B) each comprising three apparently healthy male volunteers who gave their written informed consent. The clinical part of the study was conducted in compliance with the ICH Guideline and the EC principles of good clinical practice (GCP). An approximately 0.5 ml dilution of CPF in ethanol was applied to an area of approximately 100 cm(2) of the volar aspect of the forearm, resulting in doses of either 5 mg (A) or 15 mg (B) of CPF per study subject. Duration of dermal exposure was 4 h, after which the non-absorbed fraction was washed off. The following samples were collected at pre-determined intervals for the determination of either CPF or its metabolite TCP: dosing solutions, wash-off fractions and urine samples collected up to 120 h after dosing. RESULTS: A relatively large fraction of CPF (42%-67% of the applied dose) was washed off from the exposed skin area. Application of either 5 mg (A) or 15 mg CPF (B) resulted in the total urinary excretion of 131.8 microg (A) or 115.6 microg (B) of TCP 120 h after dosing. This indicated that 4.3% of the applied dose has been absorbed (A), while in group (B) no significant increase in urinary TCP (115.6 microg) was established. The latter indicates that an increase in the dermal dose at a fixed area does not increase absorption, which suggests that the percutaneous penetration rate was constant. Further, it was observed that the clearance of CPF by the body was not completed within 120 h, suggesting that CPF or TCP was retained by the skin and/or accumulated in the body. A mean elimination half-life of 41 h was established. CONCLUSION: The results show that daily occupational exposure to CPF may result in accumulation of CPF and/or its metabolites, possibly resulting in adverse effects.


Assuntos
Clorpirifos/farmacocinética , Praguicidas/farmacocinética , Absorção Cutânea , Adulto , Clorpirifos/administração & dosagem , Clorpirifos/urina , Experimentação Humana , Humanos , Masculino , Exposição Ocupacional , Praguicidas/urina
7.
Environ Toxicol Pharmacol ; 20(3): 431-42, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21783623

RESUMO

The health risks of inhalation exposure to volatile organic solvents may not only depend on the total external dose, but also on the pattern of exposure. It has been suggested that exposure to regularly occurring peak concentrations may have a stronger impact on the brain than constant exposure at the same average level. Recent animal experimental studies conducted in our laboratory using relatively high concentrations of toluene have shown different effects on discrimination performance and motor activity during and after exposure, depending on the exposure scenario. Relevance of these findings for man was evaluated in a volunteer study in which 11 healthy men (age 20-49 years) were exposed by inhalation for 4h to either a constant concentration of 40ppm toluene or to three 30-min exposure peaks at 110ppm during this 4h period. Selected tests from the Neurobehavioural Evaluation System (NES) were performed repeatedly during and after exposure. Blood concentrations of toluene as well as urinary o-cresol excretion were measured at relevant time points. The results show that toluene concentration in blood increased during constant exposure and fluctuated during occupationally relevant peak exposures. Presumably, brain concentrations showed similar qualitative patterns. No clear changes were observed on neurobehavioural measures of motor performance, attention, perceptual coding and memory, or on measures of mood and affect. The exposure conditions do not seem to induce significant acute changes in central nervous system function similar to those observed at much higher concentrations in animals, although a statistical correlation was found between one motor performance test (Finger Tapping Test with alternating hands) and blood toluene concentrations. Urinary o-cresol excretion appeared to be significantly higher during the first 2h after exposure.

8.
Food Chem Toxicol ; 42(11): 1885-91, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15350687

RESUMO

In the organism of mammals, important detoxification pathways of arylamines are catalysed by N-acetyltransferase 2 (NAT2). A recent case-control epidemiology study suggested that human NAT2 slow acetylators exposed to oxidative hair dyes may be at greater risk to develop bladder cancer. We therefore profiled urinary [(14)C]-metabolites and NAT2 genotype in eight human subjects following treatment with a dark-shade oxidative hair dye containing [(14)C]-para-phenylenediamine (PPD). Genotyping identified three subjects as slow, and five subjects as intermediate NAT2 acetylators. Within 24 h after treatment, the study subjects excreted a mean total of 0.43+/-0.24% of the applied [(14)C] in the urine, where five different metabolites were found. The major urinary metabolites were concluded to be N-mono-acetylated and N,N'-diacetylated PPD. They were present in all urine samples and amounted to 80-95% of the total urinary [(14)C]. Another metabolite, possibly a glucuronic acid conjugate, was found in 6/8 urine samples at 5-13% of the total urinary [(14)C]. All metabolites appeared to be related to PPD, no evidence of the presence of high-molecular weight dye-intermediates or corresponding metabolites was found. The metabolite profile in the study subjects showed no significant differences between the NAT2 intermediate and NAT2 slow acetylator subgroups. Urine of NAT2 slow acetylators contained N-mono-acetylated-PPD at 42.2+/-10.2% and N,N'-di-acetylated-PPD at 54.1+/-7.6% of total urinary radioactivity, while the corresponding values of intermediate acetylators were 46.0+/-8.9% and 45.7+/-9.9%, respectively. Overall, our results suggest that the human acetylation rate of PPD after topical application is independent of the NAT2 genotype status, most likely due to metabolism by epidermal NAT1 prior to systemic absorption.


Assuntos
Arilamina N-Acetiltransferase/genética , Tinturas para Cabelo/efeitos adversos , Tinturas para Cabelo/metabolismo , Fenilenodiaminas/urina , Neoplasias da Bexiga Urinária/etiologia , Absorção , Acetilação , Administração Tópica , Adolescente , Adulto , Arilamina N-Acetiltransferase/metabolismo , Radioisótopos de Carbono , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Projetos Piloto , Neoplasias da Bexiga Urinária/genética
9.
Food Chem Toxicol ; 42(8): 1227-36, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15207372

RESUMO

We investigated the absorption of a commercial [14C]-PPD-containing oxidative dark-shade hair dye in human volunteers as well as in vitro using human or pig ear skin. The hair of eight male volunteers was cut to a standard length, dyed, washed, dried, clipped and collected. Hair, washing water, materials used in the study and a 24-h scalp wash were collected for determination of radioactivity. Blood, urine and faeces were analysed up to 120 h after hair dyeing. An identical [14C]-PPD-containing hair dye formulation was applied in vitro for 0.5 h to human and pig ear skin, and radioactivity was determined in skin compartments after 24 h. In humans, the recovery rate was 95.7+/-1.5% of the applied radioactivity. Washing water, cut hair, gloves, paper towels, caps or scalp wash contained a total of 95.16+/-1.46% of the applied [14C]. Absorbed radioactivity amounted to 0.50+/-0.24% in the urine and 0.04+/-0.04% in the faeces, corresponding to a mean of 7.0+/-3.4 mg [14C]-PPD-equivalents absorbed. Within 24 h after application, most of the radioactivity was eliminated. The Cmax of [14C]-PPD-equivalents in the plasma was 0.087 microgeq/ml, the Tmax was approximately 2 h, and the mean the AUC(0-12h) was 0.67 microgeq h/ml. In vitro tests in human or pig skin found total absorbed amounts of 2.4+/-1.6% (10.6+/-6.7 microgeq/cm2) or 3.4+/-1.7% (14.6+/-6.9 microgeq/cm2), respectively. Percentage-based in vitro results were considerably higher than corresponding in vivo data, whereas, in units of microg/cm2, they corresponded to a total absorbed amount of 7.40 or 10.22 mgeq for human or pig skin, respectively. All results suggested that hair dyeing with oxidative hair dyes produces minimal systemic exposure that is unlikely to pose a risk to human health.


Assuntos
Tinturas para Cabelo/farmacocinética , Fenilenodiaminas/farmacocinética , Absorção Cutânea/fisiologia , Adolescente , Adulto , Animais , Ensaios Clínicos como Assunto , Difusão , Orelha Externa/metabolismo , Fezes/química , Cabelo/química , Humanos , Técnicas In Vitro , Masculino , Oxirredução , Fenilenodiaminas/urina , Suínos
10.
Toxicol Lett ; 134(1-3): 125-32, 2002 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-12191870

RESUMO

Malathion was applied to roses in three Finnish greenhouses by hand held lance sprayers. The potential dermal exposure of applicators to this insecticide was measured. Total urine production of each applicator was also collected up to 24 h post application. In the urine samples the specific metabolite of malathion, malathion monocarboxylic acid (MMA), and the creatinine content were determined. The potential dermal exposure results show that during the application of malathion, the applicators' lower limbs accounted, on average, for 48%, while the upper limbs accounted for 19% of the potential dermal exposure. Moreover, hands and chest and back and head regions accounted for 30 and 3%, respectively. Based on the urine measurements, it was observed that the excretion of MMA was very rapid reaching a maximum at about 6-7 h after the completion of the application. In the urine samples collected, MMA was found to be present in relatively small amounts.


Assuntos
Agricultura , Monitoramento Ambiental/métodos , Inseticidas/farmacocinética , Malation/farmacocinética , Exposição Ocupacional/análise , Ácidos/urina , Biomarcadores/urina , Feminino , Humanos , Inseticidas/urina , Malation/urina , Masculino , Absorção Cutânea
11.
Regul Toxicol Pharmacol ; 35(2 Pt 1): 198-208, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12052004

RESUMO

The validity of in vitro and in vivo methods for the prediction of percutaneous penetration in humans was assessed using the fungicide ortho-phenylphenol (OPP) (log Po/w 3.28, MW 170.8, solubility in water 0.7 g/L). In vivo studies were performed in rats and human volunteers, applying the test compound to the dorsal skin and the volar aspect of the forearm, respectively. In vitro studies were performed using static diffusion cells with viable full-thickness skin membranes (rat and human), nonviable epidermal membranes (rat and human), and a perfused pig ear model. For the purpose of conducting in vitro/in vivo comparisons, standardized experimental conditions were used with respect to dose (120 microg OPP/cm(2)), vehicle (60% aqueous ethanol), and exposure duration (4 h). In human volunteers, the potentially absorbed dose (amount applied minus dislodged) was 105 microg/cm(2), while approximately 27% of the applied dose was excreted with urine within 48 h. In rats these values were 67 microg/cm(2) and 40%, respectively. In vitro methods accurately predicted human in vivo percutaneous absorption of OPP on the basis of the potential absorbed dose. With respect to the other parameters studied (amount systemically available, maximal flux), considerable differences were observed between the various in vitro models. In viable full-thickness skin membranes, the amount systemically available and the potentially absorbed dose correlated reasonably well with the human in vivo situation. In contrast the K(p)/maximal flux considerably underestimated the human in vivo situation. Although epidermal membranes overestimated human in vivo data, the species differences observed in vivo were reflected correctly in this model. The data generated in the perfused pig ear model were generally intermediate between viable skin membranes and epidermal membranes.


Assuntos
Compostos de Bifenilo/farmacocinética , Fungicidas Industriais/farmacocinética , Absorção Cutânea , Administração Cutânea , Adulto , Animais , Animais não Endogâmicos , Compostos de Bifenilo/administração & dosagem , Relação Dose-Resposta a Droga , Epiderme/metabolismo , Feminino , Fungicidas Industriais/administração & dosagem , Humanos , Técnicas In Vitro , Masculino , Membranas/metabolismo , Permeabilidade , Ratos , Ratos Wistar , Suínos
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