Water, soap, and hand-disinfectant exposure during the COVID-19 pandemic and self-reported hand eczema in frontline workers: A cross-sectional study.

BACKGROUND: During the COVID-19 pandemic, increased hand hygiene practices were implemented. Impaired skin health on the hands among healthcare workers has been reported previously. Knowledge of how worker in other occupations have been affected is scarce. OBJECTIVES: To investigate self-reported hand water-, and soap exposure and use of hand disinfectants, and hand eczema (HE) in frontline workers outside the hospital setting and in IT personnel during the COVID-19 pandemic. METHODS: In this cross-sectional study, a questionnaire was sent out between 1 March and 30 April in 2021, to 6060 randomly selected individuals representing six occupational groups. RESULTS: A significant increase in water exposure and hand disinfectant use was shown: Relative position (RP) 19; 95% confidence interval (CI) 0.17-0.21 and RP = 0.38: 95% CI 0.36-0.41, respectively. Newly debuted HE was reported by 7.4% of the population, more frequently among frontline workers (8.6%) compared to IT personnel (4.9%). CONCLUSIONS: Water and soap exposure and use of hand disinfectants increased during COVID-19 pandemic, which may increase the risk of hand eczema. This highlights the importance of communication and implementation of preventive measures to protect the skin barrier also in occupations other than healthcare workers.

Cobalt nanoparticles cause allergic contact dermatitis in humans.

BACKGROUND: Cobalt (Co) causes allergic contact dermatitis (ACD) and the emerging use of Co nanoparticles (CoNPs) warrants gaining further insight into its potential to elicit ACD in sensitized individuals. OBJECTIVES: The aims of the study were to clarify to what extent CoNPs may elicit ACD responses in participants with Co contact allergy, and to evaluate whether the nanoparticles cause a distinct immune response compared with cobalt chloride (CoCl2) in the skin reactions. METHODS: Fourteen individuals with Co contact allergy were exposed to CoNPs, CoCl2, a Co-containing hard-metal disc (positive control), and an empty test chamber (negative control) by patch testing. Allergic responses were evaluated clinically by a dermatologist at Days 2, 4 and 7. At Day 2, patch-test chambers were removed, and remaining test-substance and skin-wipe samples were collected for inductive-coupled plasma mass spectrometry (ICP-MS) analysis. Additionally, skin biopsies were taken from patch-test reactions at Day 4 for quantitative real-time polymerase chain reaction analysis, histopathology and ICP-MS analysis of Co skin penetration. RESULTS: Patch testing with CoNPs elicited allergic reactions in Co-sensitized individuals. At all timepoints, clinical assessment revealed significantly lower frequencies of positive patch-test reactions to CoNPs compared with CoCl2 or to the positive control. CoNPs elicited comparable immune responses to CoCl2. Chemical analysis of Co residues in patch-test filters, and on skin, shows lower doses for CoNPs compared with CoCl2. CONCLUSIONS: CoNPs potently elicit immune responses in Co-sensitized individuals. Even though patch testing with CoNPs resulted in a lower skin dose than CoCl2, identical immunological profiles were present. Further research is needed to identify the potential harm of CoNPs to human health.

A novel approach to monitor skin permeation of metals in vitro.

How metals permeate skin is poorly understood. Risk assessments tend to take default approaches to account for the dermal route, often using numbers of questionable relevance. Moreover, simultaneous exposure to multiple metals may affect the permeation of individual metals. To investigate this, we developed an experimental setup where receptor medium circulates directly from a conventional diffusion cell for in vitro skin absorption into an inductively coupled plasma mass spectrometer (ICP-MS), enabling continuous measurement of metal concentration. Full-thickness piglet skin was used as diffusion barrier, artificial sweat as donor medium and phosphate buffered saline as receptor medium. Percutaneous absorption from donor medium containing 2 mmol/L of nickel, cobalt, or chromium or all three combined was monitored for 2 h. Metals retained in skin were quantified post-exposure. Percutaneous absorption of nickel was faster in single than in combined exposure; for cobalt and chromium no such difference was apparent. Similar amounts of the three metals were retained in skin after single exposure, and retention was consistently higher for each metal after combined exposure. This study provides proof-of-concept for a method that reliably detects concentration changes in physiologically relevant medium. It may shed light on skin absorption and permeation kinetics of metals and risks associated with metal exposure.

Nickel deposition and penetration into the stratum corneum after short metallic nickel contact: An experimental study.

BACKGROUND: Knowledge about the skin deposition and penetration of nickel into the stratum corneum (SC) after short contact with metallic items is limited. OBJECTIVE: To quantify nickel skin deposition and penetration into the SC after short contact with metallic nickel. METHODS: Sixteen nickel-allergic participants and 10 controls were exposed to 3 pure nickel discs and 1 aluminium disc on each volar forearm for 3 × 10 minutes. Before exposure, 1 forearm was irritated with 0.5% sodium lauryl sulfate under 24-hour occlusion. Immediately, as well as 24 and 72 hours after metallic disc exposure, outer SC layers were removed with adhesive tapes and the nickel content was measured. RESULTS: Nickel deposition and SC penetration capable of eliciting allergic nickel dermatitis were found immediately and after 24 hours. Significantly higher nickel amounts were found on normal skin and in the SC of nickel-allergic participants than in controls both immediately and after 24 hours, and on irritated skin immediately after exposure. CONCLUSIONS: Nickel deposition and SC penetration is considerable after nickel skin exposure of 3 × 10 minutes. Combined with the allergic responses resulting from the same exposures reported previously, this study highlights that short skin exposure to nickel-releasing items may cause allergic nickel dermatitis.

Neglected exposure route: cobalt on skin and its associations with urinary cobalt levels.

OBJECTIVES: Cobalt (Co) exposure is associated with adverse health effects including skin sensitisation, asthma and interstitial lung fibrosis. Exposure to Co in industrial settings is often assessed using air samples or biomonitoring in urine. Skin exposure is rarely measured. Aim of this study was to quantify and compare the importance of Co skin exposure and respiratory exposure in determining urinary Co concentrations. METHODS: Co skin exposure was measured in 76 hard metal workers by acid wipe sampling before and at the end of work shifts. Spot urine was collected during a 24-hour period from the start of a shift. Respiratory exposure was measured by personal inhalable dust sampling during a shift in 30 workers. Co was analysed by inductively coupled plasma mass spectrometry. RESULTS: Quantile regression modelling showed that a doubling of Co on skin before or at the end of shift increased the median urinary concentration of Co by 70% (p<0.001) or 32% (p<0.001), respectively. A doubling of Co in air increased median urinary Co by 38% (p<0.001). Co skin exposures were still significantly associated with urinary Co after excluding a group of workers with high respiratory exposure (33%, p=0.021 and 17%, p=0.002). CONCLUSIONS: The results indicate an association between Co skin exposure and urinary Co concentrations. This should be considered when using urinary Co as a biomarker of exposure.

Contamination of skin and surfaces by cobalt in the hard metal industry.

BACKGROUND: It is well known that hard metal workers have historically been affected by contact allergy to cobalt. Knowledge is sparse about occupational skin exposure to cobalt, in terms of skin doses and sources of exposure, which could be used to improve protection of workers. OBJECTIVES: To improve knowledge about skin doses and sources of skin exposure to cobalt within hard metal production, thereby facilitating better protection of workers. METHODS: Forty workers were sampled on the index finger by acid wipe sampling after 2 hours of work. The samples were analysed with inductively coupled plasma mass spectrometry. Cobalt spot testing was performed in the work environment. RESULTS: The highest skin doses were found among raw material workers. Skin doses among other production workers were also significant. Most office workers had low, but measurable, levels of cobalt on the skin. Glove use varied between workers. Cobalt was found on production equipment, on items in the canteen area, and on handles and buttons throughout the company. CONCLUSIONS: Cobalt skin doses were prominent, and originated from contact with raw materials, sintered materials, and contaminated surfaces. Cobalt was present on surfaces outside production areas. Companies need to identify and reduce skin exposure for protection of workers.

Development, validation and testing of a skin sampling method for assessment of metal exposure.

BACKGROUND: Nickel, cobalt and chromium are frequent skin sensitizers. Skin exposure results in eczema in sensitized individuals, the risk being related to the skin dose. OBJECTIVES: To develop a self-sampling method for quantification of skin exposure to metals, to validate the method, and to assess its feasibility. METHODS: Defined metal doses (0.01-5 µg) were applied to the fingers of 5 participants. Skin areas (2 cm2 ) were sampled with 1% HNO3 , either as 0.1 ml on a swab, or as 0.5 ml on a wipe. Furthermore, 17 participants performed self-sampling by swab after 2 h of leisure activity. Samples were extracted in 1% HNO3 and analysed by inductively coupled plasma mass spectrometry. RESULTS: The sampling efficiency by swab was 46%, as compared with 93% for acid wipe sampling, for all tested doses. Most metal from the skin dose was detected in the first swab (33-43%). Despite lower sampling efficiency by swab, skin doses of metals following 2 h of leisure activity without hand washing were quantified in all participants, and ranged from 0.0016 to 0.15 µg/cm2 , from 0.00014 to -0.0020 µg/cm2 and from 0.00048 to -0.027 µg/cm2 for nickel, cobalt, and chromium, respectively. CONCLUSIONS: The results indicate a future potential of skin sampling by swab to detect and monitor metals on skin by self-sampling. This will contribute to better knowledge of metal skin exposure among dermatitis patients, workers, and the general population.

Testing in artificial sweat - Is less more? Comparison of metal release in two different artificial sweat solutions.

Metal release from materials immersed in artificial sweat can function as a measure of potential skin exposure. Several artificial sweat models exist that, to various degree, mimic realistic conditions. Study objective was to evaluate metal release from previously examined and well characterized materials in two different artificial sweat solutions; a comprehensive sweat model intended for use within research, based on the composition of human sweat; and the artificial sweat, EN1811, intended for testing compliance with the nickel restriction in REACH. The aim was to better understand whether there are advantages using either of the sweat solutions in bio-elution testing of materials. Metal release in two different artificial sweat solutions was compared for discs of a white gold alloy and two hard metals, and a rock drilling insert of tungsten carbide at 1 h, 24 h, 1 week and 1 month. The released amount of metal was analysed by means of inductively coupled plasma mass spectrometry. Similar levels of released metals were measured from test materials in the two different artificial sweat solutions. For purposes in relation to legislations, it was concluded that a metal release test using a simple artificial sweat composition may provide results that sufficiently indicate the degree of metal release at skin contact.

Allergy risks with laptop computers - nickel and cobalt release.

BACKGROUND: Laptop computers may release nickel and cobalt when they come into contact with skin. Few computer brands have been studied. OBJECTIVES: To evaluate nickel and cobalt release from laptop computers belonging to several brands by using spot tests, and to quantify the release from one new computer by using artificial sweat solution. METHODS: Nickel and cobalt spot tests were used on the lid and wrist supports of 31 laptop computers representing five brands. The same surfaces were tested on all computers. In addition, one new computer was bought and dismantled for release tests in artificial sweat according to the standard method described in EN1811. RESULTS: Thirty-nine per cent of the laptop computers were nickel spot test-positive, and 6% were positive for cobalt. The nickel on the surface could be worn off by consecutive spot testing of the same surface. The release test in artificial sweat of one computer showed that nickel and cobalt were released, although in low concentrations. CONCLUSIONS: As they constitute a potential source of skin exposure to metals, laptop computers should qualify as objects to be included within the restriction of nickel in REACH, following the definition of 'prolonged skin contact'. Skin contact resulting from laptop use may contribute to an accumulated skin dose of nickel that can be problematic for sensitized individuals.

Snapshot of cobalt, chromium and nickel exposure in dental technicians.

BACKGROUND: It is not fully understood where and how people are exposed to sensitizing metals. Much can be learnt from studying occupational settings where metals are handled. OBJECTIVES: To quantify cobalt (Co), chromium (Cr) and nickel (Ni) exposure on the skin and in the air, and urine levels, in dental technicians working with tools and alloys that may result in skin and respiratory exposure. METHODS: The metal skin dose was quantified with acid wipe sampling in dental technicians (n = 13). Air exposure was monitored by personal air sampling. Spot urine samples were collected for 24 h. Metals were analysed with inductively coupled plasma mass spectrometry. RESULTS: Before work, Co was detected on the skin of 10 participants (0.00025-0.0039 µg/cm2 ), and Cr (0.00051-0.011 µg/cm2 ) and Ni (0.0062-0.15 µg/cm2 ) on the skin of all participants. After a 2-h period without hand washing, CoCr-exposed participants had more Co on the skin (p = 0.004) than non-CoCr-exposed participants. Co was found in 10 air samples (0.22-155 µg/m3 ), Cr in nine (0.43-71 µg/m3 ), and Ni in four (0.48-3.7 µg/m3 ). Metal urine concentrations were considered to be normal. CONCLUSIONS: Dental technicians were exposed to Co, Cr and Ni on the skin and through the air, which was not reflected in the urine concentrations in this study. Cobalt skin doses may potentially elicit allergic contact dermatitis and cause sensitization.

Elicitation threshold of cobalt chloride: analysis of patch test dose-response studies.

BACKGROUND: Cobalt is a strong skin sensitizer (grade 5 of 5 in the guinea-pig maximization test) that is used in various industrial and consumer applications. To prevent sensitization to cobalt and elicitation of allergic cobalt dermatitis, information about the elicitation threshold level of cobalt is important. OBJECTIVE: To identify the dermatitis elicitation threshold levels in cobalt-allergic individuals. MATERIALS AND METHODS: Published patch test dose-response studies were reviewed to determine the elicitation dose (ED) levels in dermatitis patients with a previous positive patch test reaction to cobalt. A logistic dose-response model was applied to data collected from the published literature to estimate ED values. The 95% confidence interval (CI) for the ratio of mean doses that can elicit a reaction in 10% (ED(10)) of a population was calculated with Fieller's method. RESULTS: On the basis of five included studies, the ED10 values of aqueous cobalt chloride ranged between 0.0663 and 1.95 µg cobalt/cm(2), corresponding to 30.8-259 ppm. CONCLUSIONS: Our analysis provides an overview of the doses of cobalt that are required to elicit allergic cobalt contactdermatitis in sensitized individuals, and thereby the basis for future prevention of cobalt allergy.

Short and frequent skin contact with nickel.

BACKGROUND: The existing EU nickel restriction does not sufficiently protect the population from skin exposure to nickel. Better understanding is needed of the extent to which short and frequent contact with nickel-releasing items contributes to nickel deposition on skin. OBJECTIVES: To quantify nickel skin exposure from short and frequent contact with nickel-releasing materials. MATERIALS/METHODS: Sequences of short contact events were assessed in (i) touch tests for measurement of nickel skin dose, (ii) wipe tests to similarly quantify the nickel release during a touch, and (iii) immersion tests in artificial sweat, for nickel-containing alloys and pure nickel. RESULTS: Nickel skin doses from a single touch were 0.024-4.7 µg/cm(2) for all materials. Touching or wiping five untouched surfaces resulted in more accumulated nickel than five repeated touches of the same surface. The released amounts of nickel were generally lower at immersion, but increased with the number of repeated immersion periods. CONCLUSIONS: Nickel skin doses were quantified after one single touch for all study materials. Touch tests, and potentially wipe tests as a proxy for skin dose measurements, are preferred to immersion tests for the assessment of short and frequent skin contact with nickel.

Cobalt skin dose resulting from short and repetitive contact with hard metals.

BACKGROUND: Many daily contacts with metallic items are short and repetitive, and result in metal release; material, sweat, friction and wear may all be important. OBJECTIVES: To study cobalt release and skin deposition as a result of many short and repetitive contacts with two cobalt-containing materials. MATERIALS/METHODS: Study participants (n = 5) handled two types of hard metal disc (Co 6% and Co 15% Cr 0.6%) for 30 min. Deposited cobalt skin doses were measured with acid wipe sampling and chemical analysis. Cobalt release from the hard metal discs in artificial sweat was measured under conditions simulating those present during the handling of discs. RESULTS: Average cobalt skin doses from discs containing 6% Co and 15% Co 0.6% Cr were 1.1 µg/cm(2) [standard deviation (SD) 0.4 µg/cm(2) ] and 0.7 µg/cm(2) (SD 0.5 µg/cm(2) ), respectively. More cobalt was released from hard metal discs containing 6% Co [11.4 µg/cm(2) (SD 1.2 µg/cm(2) )] than from discs containing 15% Co 0.6% Cr [4.8 µg/cm(2) (SD 0.6 µg/cm(2) )]. 10% to 15% of the potentially available cobalt was deposited on the skin during handling. CONCLUSIONS: It is likely that the cobalt deposited as a result of short and repetitive contact with hard metals may cause harm. Research regarding cobalt exposure, metal release and the deposition of skin-sensitizing metals resulting from short and repetitive contact is needed for a better understanding of the allergy risk.

The cobalt spot test--further insights into its performance and use.

BACKGROUND: A spot test was recently developed for easy and rapid testing to detect whether cobalt is available on surfaces in contact with skin. OBJECTIVES: To explore the potential use of the cobalt spot test as a tool for skin dose assessment, and to verify the sensitivity under laboratory conditions. METHODS: A cobalt dilution series (cobalt standards mixed with cobalt spot test reagent solution) was prepared to determine the threshold for colour change. Defined doses of cobalt were applied to the fingers of 5 volunteers. Acid wipe sampling was used to measure the recovery of applied cobalt skin doses on one hand, and cobalt-exposed areas on the other hand were spot tested. RESULTS: A weak colour gradient was visible from approximately 1 to 1.5 µg cobalt/ml in the dilution series. For a skin dose of 0.125 µg cobalt/cm(2) , 80% of the cobalt dose was collected by acid wipe sampling. Spot tests gave positive results in all cases (n = 5). CONCLUSIONS: The cobalt spot test can be used to show cobalt on the skin. More experience is needed to understand and describe the most suitable test conditions.

New UK nickel-plated steel coins constitute an increased allergy and eczema risk.

BACKGROUND: Nickel-plated steel coins have recently been introduced in the United Kingdom. OBJECTIVES: To compare the performance and allergy risk of the new nickel-plated coins (five and ten pence) with those of the cupro-nickel coins being replaced. MATERIALS AND METHODS: Coin handling studies with assessment of skin exposure and metal release in artificial sweat were performed. Six volunteers participated. RESULTS: The amount of nickel deposited onto skin during the handling of nickel-plated coins for 1 hr was 7.5 µg/cm(2) , four times higher than that from cupro-nickel coins. The nickel content in the oxidized surface of nickel-plated coins was higher, explaining the higher skin dose. Initial nickel release rates were 10-27 times higher than 1-week rates, emphasizing that brief and repeated contact results in significant nickel exposure. CONCLUSIONS: Nickel-plated coins deposit higher levels of nickel onto skin than cupro-nickel coins, and hence pose an increased allergy risk. One-week release in artificial sweat is not suitable for determining the risk of handling items with high nickel release that come into short, repeated contact with the skin. The nickel skin dose is recommended for risk assessment. UK citizens are now, because of this change in coinage, unnecessarily exposed to higher levels of nickel on the skin. This is of public health concern.

Gold Nanoparticles Dissolve Extracellularly in the Presence of Human Macrophages.

INTRODUCTION: Gold nanoparticles (AuNPs) have the potential to be used in various biomedical applications, partly due to the inertness and stability of gold. Upon intravenous injection, the NPs interact with the mononuclear phagocyte system, first with monocytes in the blood and then with macrophages in tissue. The NP-macrophage interaction will likely affect the stability of the AuNPs, but this is seldom analyzed. This study aimed to elucidate the role of macrophages in the biodissolution of AuNPs and underlying mechanisms. METHODS: With an in vitro dissolution assay, we used inductively coupled plasma mass spectrometry to quantitatively compare the dissolution of 5 and 20 nm AuNPs coated with citrate or PEG in cell medium alone or in the presence of THP1-derived macrophages at 24 hours. In addition, we analyzed the cell dose, compared extra- and intracellular dissolution, and explored the possible role of reactive nitrogen species. RESULTS: The results showed a higher cellular dose of the citrate-coated AuNPs, but dissolution was mainly evident for those sized 5 nm, irrespective of coating. The macrophages clearly assisted the dissolution, which was approximately fivefold higher in the presence of macrophages. The dissolution, however, appeared to take place mainly extracellularly. Acellular experiments demonstrated that peroxynitrite can initiate oxidation of gold, but a ligand is required to keep the gold ions in solution. CONCLUSION: This study suggests extracellular dissolution of AuNPs in the presence of macrophages, likely with the contribution of the release of reactive nitrogen species, and provides new insight into the fate of AuNPs in the body.

A Case Study of Brass Foundry Workers' Estimated Lead (Pb) Body Burden from Different Exposure Routes.

OBJECTIVES: The most pronounced occupational exposure routes for lead (Pb) are inhalation and gastrointestinal uptake mainly through hand-to-mouth behaviour. Skin absorption has been demonstrated for organic Pb compounds, but less is known about inorganic Pb species. Several legislative bodies in Europe are currently proposing lowering biological exposure limit values and air exposure limits due to new evidence on cardiovascular effects at very low blood Pb levels. In light of this, all exposure routes in occupational settings should be revisited to evaluate how to lower the overall exposure to Pb. METHODS: The aim of the study was to investigate the possible exposure routes in workers operating computer numerical control-machines in a brass foundry and specifically to understand if metal cutting fluids (MCFs) used by the workers could lead to skin absorption of Pb. The different bronze alloys at the facility may contain up to 20% Pb. After obtaining written informed consent from the workers (n = 7), blood, skin wipes, and personal air samples were collected. In addition, MCFs used on the day of exposure measurements were collected for in vitro skin absorption studies using stillborn piglet skin mounted in static Franz diffusion cells (n = 48). All samples were analysed for Pb content using inductively coupled plasma mass spectrometry. RESULTS: Pb air concentration (<0.1-3.4 µg m-3) was well below the Swedish occupational exposure limit value. Blood Pb was in the range of <0.72-33 µg dl-1, and Pb on skin surfaces, after performing normal work tasks during 2 h, was in the range of 0.2-48 µg cm-2. Using the MCFs in diffusion cells showed that skin absorption had occurred at very low doses, and that up to 10% of the Pb content was present in the skin after 24 h exposure. Using these results in the US EPA adult lead model, we could estimate a contribution to blood Pb from the three exposure routes; where hand-to-mouth behaviour yielded the highest contribution (16 µg Pb dl-1 blood), followed by skin absorption (3.3-6.3 µg Pb dl-1 blood) and inhalation (2.0 µg Pb dl-1 blood). CONCLUSIONS: This case study shows that MCF may lead to skin absorption of inorganic Pb and contribute to a systemic dose (quasi-steady state). Furthermore, even though good hand hygienic measures were in place, the workers' skin exposure to Pb is in all likelihood an important contributor in elevating blood Pb levels. Skin exposure should thus be monitored routinely in workers at facilities handling Pb, to help reducing unnecessary occupational exposure.

Surface characteristics, copper release, and toxicity of nano- and micrometer-sized copper and copper(II) oxide particles: a cross-disciplinary study.

An interdisciplinary and multianalytical research effort is undertaken to assess the toxic aspects of thoroughly characterized nano- and micrometer-sized particles of oxidized metallic copper and copper(II) oxide in contact with cultivated lung cells, as well as copper release in relevant media. All particles, except micrometer-sized Cu, release more copper in serum-containing cell medium (supplemented Dulbecco's minimal essential medium) compared to identical exposures in phosphate-buffered saline. Sonication of particles for dispersion prior to exposure has a large effect on the initial copper release from Cu nanoparticles. A clear size-dependent effect is observed from both a copper release and a toxicity perspective. In agreement with greater released amounts of copper per quantity of particles from the nanometer-sized particles compared to the micrometer-sized particles, the nanometer particles cause a higher degree of DNA damage (single-strand breaks) and cause a significantly higher percentage of cell death compared to cytotoxicity induced by micrometer-sized particles. Cytotoxic effects related to the released copper fraction are found to be significantly lower than the effects related to particles. No DNA damage is induced by the released copper fraction.

Macrophage-Assisted Dissolution of Gold Nanoparticles.

Gold nanoparticles (AuNPs) are readily functionalized and considered biocompatible making them useful in a wide range of applications. Upon human exposure, AuNPs will to a high extent reside in macrophages, cells that are designed to digest foreign materials. To better understand the fate of AuNPs in the human body, their possible dissolution needs to be explored. In this study, we tested the hypothesis that macrophages, and especially stimulated macrophages, can impact the dissolution of AuNPs in a size-dependent manner. We developed an in vitro method to compare the dissolution of citrate coated 5 and 50 nm-sized AuNPs, in terms of released gold ions as measured by inductive coupled mass spectrometry (ICP-MS), in (i) cell medium (alone) (ii) in medium with macrophages present and (iii) in medium with lipopolysaccharide (LPS) triggered macrophages (simulating inflammatory conditions). We found an evident, time-dependent dissolution of AuNPs in cell medium, corresponding to 3% and 0.6% of the added amounts of 5 and 50 nm AuNPs, respectively, after 1 week (168 h) of incubation. The dissolution of 5 nm AuNPs was further increased to 4% in the presence of macrophages and, most strikingly, 14% was dissolved in case of LPS-triggering. In contrast, only a minor increase was observed for 50 nm AuNPs after 1 week in the presence of LPS-triggered macrophages compared to medium alone. Dissolution experiments in the absence of cells highlighted the importance of biomolecules. Our findings thus show dissolution of citrate coated AuNPs that is dependent on size, presence of macrophages, and their inflammatory state. These findings have implications for understanding the transformation/dissolution and fate of AuNPs.