Including non-dietary sources into an exposure assessment of the European Food Safety Authority: The challenge of multi-sector chemicals such as Bisphenol A.

In the most recent risk assessment for Bisphenol A for the first time a multi-route aggregate exposure assessment was conducted by the European Food Safety Authority. This assessment includes exposure via dietary sources, and also contributions of the most important non-dietary sources. Both average and high aggregate exposure were calculated by source-to-dose modeling (forward calculation) for different age groups and compared with estimates based on urinary biomonitoring data (backward calculation). The aggregate exposure estimates obtained by forward and backward modeling are in the same order of magnitude, with forward modeling yielding higher estimates associated with larger uncertainty. Yet, only forward modeling can indicate the relative contribution of different sources. Dietary exposure, especially via canned food, appears to be the most important exposure source and, based on the central aggregate exposure estimates, contributes around 90% to internal exposure to total (conjugated plus unconjugated) BPA. Dermal exposure via thermal paper and to a lesser extent via cosmetic products may contribute around 10% for some age groups. The uncertainty around these estimates is considerable, but since after dermal absorption a first-pass metabolism of BPA by conjugation is lacking, dermal sources may be of equal or even higher toxicological relevance than dietary sources.

Use-patterns of personal care and household cleaning products in Switzerland.

Reliable consumer use data are needed to determine health risks posed by chemicals contained in household cleaning and personal care products. Essential information includes the amount of product applied, the frequency of use, and the site of application. To obtain such data, a survey was conducted in Switzerland to assess consumer usage patterns. The use-patterns of 12 household care products, 5 laundry products, and 22 personal care products were collected among the Swiss population (N = 759; ages 0-91) by postal questionnaire, providing for the first time in Europe comprehensive information regarding use of household cleaning and personal care products for the same study population. Apart from the investigation of use frequency, quantity, duration, and habits, also co-use analysis was performed separately for household and personal care products. Use-patterns are presented for both genders and all age groups, including children below the age of 12, who may be more vulnerable to adverse effects attributed to certain chemicals. Also, the currently missing use factors for cosmetic/baby wet wipes were assessed. Stratification of the data by gender, age and other socio-demographic factors, such as region affiliation, allowed us to identify differences between population sub-groups, emphasizing the need for region-specific exposure factors.

Value of MRI olfactory bulb evaluation in the assessment of olfactory dysfunction in Bardet-Biedl syndrome.

Olfactory bulb (OB) volume evaluation by magnetic resonance imaging (MRI) has been demonstrated to be related to olfactory dysfunction in many different diseases. Olfactory dysfunction is often overlooked in Bardet-Biedl syndrome (BBS) patients and is rarely objectively evaluated by MRI. We present a series of 20 BBS patients with olfactory dysfunction. The OB was evaluated separately and blindly by two radiologists (SR and SM) with 3 Tesla MRI imaging comparatively to 12 normal control subjects by global visual evaluation and by quantitative measurement of OB volume. In the 12 control cases OB visual evaluation was considered as normal in all cases for radiologist (SR) and in 10 cases for radiologist (SM). In the 20 BBS patients, OB visual evaluation was considered as abnormal in 18 cases for SR and in all cases for SM. OB volumetric evaluation for SR and SM in BBS patients was able to provide significant correlation between BBS and olfactory dysfunction. This study indicates that OB volume evaluation by MRI imaging like structural MRI scan for gray matter modifications demonstrates that olfactory dysfunction in BBS patients is a constant and cardinal symptom integrated in a genetical syndrome with peripheral and central olfactory structure alterations.

Ultraviolet filter contact and photocontact allergy: consumer exposure and risk assessment for octocrylene from personal care products and sunscreens.

BACKGROUND: Octocrylene (OCT) is an ultraviolet (UV) filter used in personal care products (PCPs) to prevent sun-related skin damage. OCT is photostable and has the ability to photostabilize other UV filters, which has recently led to its increased use in PCPs. Emerging clinical and experimental studies indicate that OCT is both a contact and a photocontact allergen. OBJECTIVES: To quantify OCT exposure via PCPs, including aggregate exposure that arises from concurrent use of multiple PCP categories, for use in an exposure-based quantitative risk assessment (QRA). METHODS: Probabilistic modelling of exposure was performed at an individual level simulating 1 day of concurrent and single PCP use. PCP use data obtained via a questionnaire were linked to OCT concentrations gained from chemical analyses of PCPs used by the questionnaire respondents from the German-speaking part of Switzerland (n = 1196; ages ≤ 1-97 years). Acceptable exposure levels (AELs) were calculated for OCT and compared with the computed exposure estimates. RESULTS: Overall, 19%, 33% and 79% of respondents were exposed to OCT via hand cream, face cream and sunscreen, respectively. Sunscreen was the most prevalent exposure source and largest contributor to aggregate exposure. For the study population, the overall mean and median exposure to OCT via sunscreen alone exceeded the QRA-predicted AEL of 4·9 µg cm(-2). CONCLUSIONS: Use of OCT in PCPs at levels greater than the threshold for induction of skin sensitization might lead to an increased number of sensitized individuals. It is therefore desirable to perform a new safety assessment of OCT.

Migration of Ag- and TiO2-(Nano)particles from textiles into artificial sweat under physical stress: experiments and exposure modeling.

Engineered nanoparticles (ENP) are increasingly used to functionalize textiles taking advantage, e.g., of the antimicrobial activity of silver (Ag)-ENP or the UV-absorption of titania (TiO2)-ENP. Mobilization and migration of ENPs from the textile into human sweat can result in dermal exposure to these nanoobjects and their aggregates and agglomerates (NOAA). In this study we assessed exposure to NOAA migrating from commercially available textiles to artificial sweat by an experimental setup that simulates wear-and-tear during physical activity. By combining physical stress with incubation in alkaline and acidic artificial sweat solutions we experimentally realized a worst case scenario for wearing functionalized textiles during sports activities. This experimental approach is not limited to NOAA, but can be used for any other textile additive. Out of four investigated textiles, one T-shirt and one pair of trousers with claimed antimicrobial properties were found to release Ag <450 nm in detectable amounts (23-74 µg/g/L). Textiles containing TiO2 for UV protection did not release significant amounts of TiO2 <450 nm, but the antimicrobial T-shirt released both TiO2 and Ag <450 nm. The silver was present in dissolved and particulate form, whereas TiO2 was mainly found as particulate. On the basis of our experimental results we calculated external dermal exposure to Ag and TiO2 for male and female adults per use. For silver, maximal amounts of 17.1 and 8.2 µg/kg body weight were calculated for total and particulate Ag <450 nm, respectively. For TiO2, the exposure levels amount to maximal 11.6 µg/kg body weight for total (mainly particulate) TiO2. In comparison with other human exposure pathways, dermal exposure to NOAA from textiles can be considered comparably minor for TiO2-NOAA, but not for Ag-NOAA.

Release of titanium dioxide from textiles during washing.

Nano-TiO(2) has the highest production of all nanomaterials, and pigment-TiO(2) is a commodity used on the million tons/year scale. Information on the release of TiO(2) from consumer products is therefore an important part of analyzing the potential environmental exposure to TiO(2). For this study, we investigated the release of TiO(2) from six different functional textiles during washing. TiO(2) is used in textiles because of its UV-absorbing properties and as pigment. Analysis of fiber cross sections showed that the TiO(2) was contained in the fiber matrix. The sun-protection textiles had Ultraviolet Protection Factors that were between 58 and 6100 after washing and therefore above the labeled factor of 50+. Five of the textiles (sun-protection clothes) released low amounts of Ti (0.01 to 0.06 wt % of total Ti) in one wash cycle. One textile (with antimicrobial functionality) released much higher amounts of Ti (5 mg/L, corresponding to 3.4 wt % of total Ti in one wash cycle). Size fractionation showed that about equal amounts were released as particles below and above 0.45 µm. After 10 washings, only in two textiles significantly lower Ti contents were measured. Electron microscopy showed that the TiO(2) particles released into washing solution had a roundish appearance with primary particle sizes between 60 and 350 nm that formed small aggregates with up to 20 particles. The results indicate that functional textiles release some TiO(2) particles, but that the amounts are relatively low and mostly not in the nanoparticulate range.

Characterization of silver release from commercially available functional (nano)textiles.

Silver, both in the nano as well as in other forms, is used in many applications including antimicrobial textiles. Washing of such textiles has already been identified as an important process that results in the release of silver into wastewater. This study thus investigated the release of silver from eight different commercially available silver-textiles during a washing and rinsing cycle. The silver released was size-fractionated and characterized using electron microscopy. In addition, the antimicrobial functionality of the textiles was tested before and after washing. Three of the textiles contained nanosized silver (labeled or confirmed by manufacturers' information), another used a metallic silver wire and four contained silver in undeclared form. The initial silver content of the textiles was between 1.5 and 2925mg Ag/kg. Only four of the investigated textiles leached detectable amounts of silver, of which 34-80% was in the form of particles larger than 450nm. Microscopic analysis of the particles released in the washing solutions identified Ti/Si-AgCl nanocomposites, AgCl nanoparticles, large AgCl particles, nanosilver sulfide and metallic nano-Ag, respectively. The nanoparticles were mainly found in highly agglomerated form. The identified nanotextiles showed the highest antimicrobial activity, whereas some of the other textiles, e.g. the one with a silver wire and the one with the lowest silver content, did not reduce the growth of bacteria at all. The results show that different silver textiles release different forms of silver during washing and that among the textiles investigated AgCl was the most frequently observed chemical form in the washwater.

Restraint reduction in orthopaedics.

Restraint reduction is a challenge, especially when working with an elderly population. This article describes one orthopaedic unit's successful restraint reduction program. The role of the nurses on the unit is discussed, along with forms that were helpful and the fact that the reduction program fit into the Performance Improvement Plan for the institution. The most frequently used and successful alternatives are discussed. A restraint/seclusion data collection form has been highlighted. Finally, areas for additional research are suggested.

Cross-polarization/magic-angle-spinning nuclear magnetic resonance in selectively 13C-labeled synthetic eumelanins.

We report a solid-state NMR study of synthetic eumelanins prepared by oxidation of 5,6-dihydroxyindole (DHI) selectively 13C-labeled at positions 2 or 3 of the indole ring. The 13C-1H couplings have been used to quantify the carbons by selecting the non-protonated and protonated carbon resonances. By comparing the data of non-labeled melanin to that obtained using [2-(13)C]- and [3-(13)C]-enriched DHI, it was possible to clearly demonstrate the high chemical reactivity of position 2 and, to a lesser extent, position 3 of the DHI unit. These two sites together are responsible for three-quarters of the proton loss during polymerization. The cross-polarization/magic-angle-spinning spectra likewise point to a partial oxidation of positions 2 and 3 to the carboxyl and carbonyl oxidation states during the formation of melanin. Furthermore, it is shown that 13C-13C dipolar interactions in [2-(13)C]-enriched DHI melanins can be observed using radiofrequency-driven dipolar recoupling (RFDR) 2D experiments. An upper limit of about 4 A for the distance between the C-2 carbons is deduced from the RFDR experiments. This result is in agreement with the basic arrangement of the different atoms expected in the DHI melanins.

A 13C solid-state NMR study of the structure and auto-oxidation process of natural and synthetic melanins.

This paper presents a 13C CP/MAS NMR study of the melanin pigments obtained through natural and synthetic origins: sepia-melanin from squid ink and three synthetic 5,6-dihydroxyindole-melanins prepared using different non-enzymatic oxidation pathways. The synthetic pigments can be distinguished from natural melanin by the absence of aliphatic carbons, thereby confirming the unreacted 3,4-dihydroxyphenylalanine and the proteinaceous origins of the aliphatic resonances in natural eumelanin. The spectra of selected non-protonated carbon resonances and those with only protonated carbon signals led to a quantitative analysis. An auto-oxidative experiment using a synthetic melanin, over a period of 130 h, has shown an unusually slow disappearance of hydrogen peroxide formed in situ. The 13C-NMR spectrum of the insoluble oxidized synthetic melanin compared to that before auto-oxidation clearly demonstrates that the oxidation process is associated with chemical changes within the pigment; i.e., carbonyl functional group formation and an increase of the non-protonated carbons fraction.

Percutaneous absorption of p-phenylene diamine during an actual hair dyeing procedure.

Synopsis An analytical method has been developed that allows the determination of p-phenylene diamine derivatives in urinary samples collected from women after hair dyeing with commercial formulations. During an on-line flash hydrolysis of the urine, a number of metabolites of p-phenylene diamine were hydrolyzed to free p-phenylene diamine, which was then determined using gas chromatography-mass spectrometry. The excretion of metabolites of p-phenylene diamine could be followed during 24 or 48 hours after the dye had been applied. Most of the p-phenylene diamine cleaved by the flash hydrolysis procedure was, in fact, involved in the N,N'-diacetyl combination. The dose excretion for p-phenylene diamine as measured by this method was comparable to that found by other authors who made use of radioactively labelled material. The present analytical method can be used to evaluate procedures intended to decrease the percutaneous absorption of p-phenylene diamine. Thus, a five- to ten-fold decrease in its penetration was observed by protecting the scalp with clay before applying the dyeing composition.

Capillary gas chromatographic analysis of human skin surface lipids after microsampling on ground-glass platelets.

Small amounts of human skin surface lipids, in the 1-20 micrograms range, sampled on ground-glass platelets are investigated using capillary gas chromatography. A first system allows the separation of the neutral lipids, up to the triglyceride fraction. A second system reveals the distribution of the free fatty acids or of the free + glyceride fatty acids, after a methylation or transesterification step. Examination of samples from nine subjects shows that the unsaturation of the free fatty acids increases during a four-day period of accumulation. Comparison of the free fatty acid fraction and the free + glyceride fatty acid fraction shows that the fraction is more saturated than the latter. It is concluded that the bacterial lipases which cleave the fatty acids from the ester bond favor the liberation of straight-chain saturated fatty acids from sebum triglycerides. This result is confirmed by comparison of the free fatty acid fraction with the glyceride fatty acid fraction separated from bulk samples of skin surface lipids from hair and scalp.

Evolution in the composition of human skin surface lipids during their accumulation on scalp and hair.

Synopsis Qualitative examination of human surface lipids collected using a surfactant solution shows that there are no significant differences between individuals when the samples are collected after one day, starting from clean hair and scalp. On the contrary, samples collected after 4 days reveal discrepancies within the population, related to the oily hair symptom. An evolution in the composition of the recovered mixture occurs during the 1-4 days accumulation period, which mainly results in an increased unsaturation of the total (free + glycerides) fatty acids fraction isolated after saponification. A two-step mechanism is proposed to account for the observed evolution: in a first step, free fatty acids are cleaved from glycerides by the well known enzymatic hydrolysis. Analytical determinations show that this process is structure dependant, the straight chain saturated acids being more readily hydrolyzable than the unsaturated and branched chain species. In a second step, free fatty acids are immobilized on the keratinic fibers, by a process which involves the formation of Ca salts. This evolution results in a decreased viscosity of the skin surface lipids and in an increase of the low temperature melting fraction of the mixture. Its extent is more or less pronounced, depending upon the individuals. Subjects who exhibit extensive evolution are affected by the oily hair symptom.

Differential thermal analysis of human sebum as a new approach to rheological behaviour.

Synopsis The oily aspect of a hair is not only the consequence of an excessive lipidic production on the scalp; the quality of the fatty mixture should also be considered. Differential scanning calorimetry (DSC) is a useful tool for qualitative examination of human sebum. The melting curves recorded using this technique characterise the seborrhoeic state of the subject, their profile being related to the clinical appreciation. Data from DSC are correlated with other physico-chemical characteristics of sebum, especially with the proportion of unsaturated fatty acids in the whole fatty acids fraction. The straight chain monoenic acids have been more closely examined. A number of positional isomers can be seen; the distribution of the C(18) isomers varies according to the seborrhoeic state of the subject.

Studies on the mutagenicity of p-phenylenediamine in Salmonella typhimurium. Presence of PCB's in rat-liver microsomal fraction induced by Aroclor.

The mutagenicity of fresh solutions of p-phenylenediamine (PPD) and Aroclor 1254 was investigated. The histidine-requiring strains of Salmonella typhimurium were used in the absence and presence of uninduced and/or Aroclor-induced rat-liver homogenate. The presence of polychlorinated biphenyls (PCBs) was also examined by chromatographic methods in Aroclor-induced rat-liver homogenate. In the absence of metabolic activation, as well as in the presence of uninduced rat-liver homogenate, PPD was not mutagenic in the strains used. In the presence of Aroclor-induced S9 a twofold increase (or less) was observed in the number of revertant colonies over those of the controls in TA1538 and TA98. There was no increase in the number of revertant colonies over those of the controls when PPD was dissolved in NH4OH solution and the solution mixed with H2O2 before the addition of S9 mix. Aroclor 1254 was not mutagenic in TA1538 or TA98. However, the presence of PCBs in Aroclor-induced rat-liver homogenate (induced S9) was identified by gas-liquid chromatography (GLC), high-performance liquid chromatography (HPLC) and gas--liquid chromatography/mass spectrometry (GC/MS).