In a 2018 survey, U.S. Food and Drug Administration (FDA) identified microbial contamination in 42 (49%) of 85 unopened tattoo and permanent makeup (PMU) inks purchased from 13 manufacturers in the ...US between November 2015 and April 2016. To confirm the results of our previous survey, we evaluated the level of microbial contamination in an additional 27 samples from 10 manufacturers from September 2017 to December 2017, including 21 unopened tattoo and PMU inks which were selected based on our previous survey results and 6 ink diluents that were not previously analysed. Aerobic plate count and enrichment culture methods from the FDA’s Bacteriological Analytical Manual revealed 11 (52%) out of 21 inks, from six manufacturers, were contaminated with micro‐organisms, with contamination levels up to 3·6 × 108 CFU per gram, consistent with our previous survey results. We identified 25 bacterial strains belonging to nine genera and 19 species. Strains of Bacillus sp. (11 strains, 44%) were dominant, followed by Paenibacillus sp. (5 strains, 20%). Clinically relevant strains, such as Kocuria rhizophila and Oligella ureolytica, were also identified, as similar to the findings in our previous survey. No microbial contamination was detected in any of the six ink diluents.
Significance and Impact of the Study: Risks of infection associated with tattoo and permanent makeup (PMU) inks contaminated with microorganisms continues to be a public health concern. This study confirms the results from our previous study showing that a high portion of tattoo and PMU inks were contaminated with micro‐organisms, including pathogenic bacteria. The results of this survey highlight the safety concerns associated with intradermal injection of microbially contaminated tattoo inks. Furthermore, this study shows the importance of continuously monitoring the levels of microbial contamination of tattoo and PMU inks marketed in the US.
Aims
Tattooing and use of permanent makeup (PMU) has dramatically increased over the last decade, with a concomitant increase in ink‐related infections. The aim of this study was to determine whether ...micro‐organisms are present, and if so, the number and their identification in the commercial tattoo and PMU inks available in the United States.
Methods and Results
We surveyed 85 unopened tattoo and PMU inks, purchased from 13 companies. We incubated 100 μl of ink samples on trypticase soy agar plates for bacterial growth, 7H10 Middlebrook medium for mycobacterial growth, and Sabouraud dextrose medium for fungal growth. In total, 42 inks were contaminated with micro‐organisms (49%). Thirty‐three inks were contaminated with bacteria, 2 inks with fungi, and 7 inks had both bacterial and fungal growth. Mycobacteria were not detected in any of the examined tattoo and PMU inks. In 26 inks, microbial concentrations ranged between 101 and 103 CFU per ml, but higher counts (>103 CFU per ml) were recorded in 16 inks. We identified 83 bacteria by their 16S rDNA sequences, including 20 genera and 49 species. Strains of Bacillus spp. (53%) were dominant, followed by Lysinibacillus fusiformis (7%) and Pseudomonas aeruginosa (5%). Thirty‐four (41%) possibly clinically relevant strains were identified, including P. aeruginosa, Dermacoccus barathri and Roseomonas mucosa, some of which have been previously reported to be associated with human skin infections.
Conclusions
The results indicate that commercial tattoo and PMU inks on the US market surveyed in this study contain a wide range of micro‐organisms, including pathogenic bacteria.
Significance and Impact of the Study
Microbial contaminants in tattoo and PMU inks are an emerging safety concern for public health. This study provides evidence that microbial contamination of tattoo and PMU inks available in the United States is more common than previously thought and highlights the importance of monitoring these products for potentially pathogenic micro‐organisms.
Considerable media attention has recently been given to novel applications for products that contain nanoscale materials. These products could have utility in several industries that market consumer ...products, including textiles, sporting equipment, cosmetics, consumer electronics, and household cleaners. Some of the purported benefits of these products include improved performance, convenience, lower cost, as well as other desirable features, when compared to the conventional products that do not contain nanoscale materials. Although there are numerous likely consumer advantages from products containing nanoscale materials, there is very little information available regarding consumer exposure to the nanoscale materials in these products or any associated risks from these exposures. This paper seeks to review a limited subset of products that contain nanoscale materials, assess the available data for evaluating the consumer exposures and potential hazards associated with these products, and discuss the capacity of U.S. regulatory agencies to address the potential risks associated with these products.
In an attempt to assess cosmetics containing ‘nontraditional’ preservatives, 93 eye area cosmetic products were selected based on labelled or marketed claims that these products were ‘green’, ...‘natural’, ‘paraben‐free’, ‘preservative‐free’ or contained nontraditional preservatives (e.g. botanical extracts). Products were analysed for water activity, pH and microbiological content, which included enumeration of aerobic micro‐organisms, detection of microbial growth after a 7‐day enrichment and identification of microbial isolates. The survey found that 60% (56/93) of the eye area cosmetics were free of microbiological growth under test conditions, 32% (30/93) showed the presence of micro‐organisms at low levels (<100 CFU per ml or g) and 8% (7/93) showed microbiological growth at higher levels (> 100 CFU per ml or g). Gram‐positive bacteria such as Bacillus and Staphylococcus were the dominant genera identified in these cosmetic products, whereas Gram‐negative species were relatively uncommon. The survey found a positive association between lower water activity cosmetics and the presence of micro‐organisms in these products. Similarly, colour cosmetics were more likely to contain micro‐organisms than noncolour cosmetics. The most represented micro‐organisms in the survey were from genus Bacillus, suggesting that the natural raw materials are the likely source of observed microbial loads.
Significance and Impact of the Study
In the United States, cosmetic products are regulated postmarket; therefore, surveillance programmes are one of FDA's most important tools for monitoring microbiological safety of cosmetics. ‘Traditional’ preservatives, such as parabens and formaldehyde releasers, are perceived unfavourably by some consumers, resulting in cosmetic manufacturers increasingly using ‘nontraditional’ preservatives. FDA conducted an analytical survey of eye area cosmetics that claimed to be free of traditional preservatives and determined microbiological loads in tested products. This study explores the association of microbial loads with the physical and chemical characteristics of the cosmetic products, and points to the limits of preservative activity in cosmetics.
Significance and Impact of the Study: In the United States, cosmetic products are regulated postmarket; therefore, surveillance programmes are one of FDA's most important tools for monitoring microbiological safety of cosmetics. ‘Traditional’ preservatives, such as parabens and formaldehyde releasers, are perceived unfavourably by some consumers, resulting in cosmetic manufacturers increasingly using ‘nontraditional’ preservatives. FDA conducted an analytical survey of eye area cosmetics that claimed to be free of traditional preservatives and determined microbiological loads in tested products. This study explores the association of microbial loads with the physical and chemical characteristics of the cosmetic products, and points to the limits of preservative activity in cosmetics.
Synopsis
In the past several years, there has been a trend in the sunscreen/cosmetics industry to replace micron‐sized titanium dioxide (TiO2) particles with nanoscale materials. The increased use of ...nanoscale TiO2 has resulted in questions about these and other nanoproducts. This study examines the effects of using nanoscale TiO2 on ultraviolet (UV) attenuation in simple to complex sunscreen formulations. UV light attenuation, product stability, and potential damage to the skin barrier were examined with both nanoscale and microscale TiO2 particles. Results indicate that none of the formulations decreased the barrier function of the skin and the best UV attenuation occurs when the TiO2 particles are stabilized with a coating and evenly distributed such as with non‐agglomerated coated nanoscale materials. This indicates that nanoscale TiO2 may have better efficacy while lacking toxicity.
Résumé
Au cours des dernières années, nous avons constaté une tendance dans l’industrie solaire/cosmétique pour le remplacement des particules micron‐taille de dioxyde de titane (TiO2) avec des matériaux de nano‐échelle. L’utilisation accrue des particules de TiO2 l’échelle du nanométre a engendré des questions sur tous les produits contenant des matériaux nano‐échelle. Cette étude examine les effets de l’utilisation de particule de TiO2 a l’échelle du nanomètre sur l’atténuation des rayons UV dans les formulations de crème solaire simple et complexe. Nous avons étudié l’atténuation de la luminosité ultraviolet (UV), la stabilité du produit et les effets sur la fonction barrière de la peau, avec les particules de TiO2 nano‐échelle et micro‐échelle. Les résultats indiquent que les particules a l’échelle du nanométre, enduits et non‐aggloméré, fournissent une excellente atténuation UV, sans diminuer la fonction barrière de la peau. Ceci suggére que les particules de TiO2 a l’échelle du nanométre ont une meilleure efficacité, sans poser des inquiétudes en ce qui concerne leur securité.
Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi‐age rat model could be used for pre‐clinical studies of comparative drug toxicity ...in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age‐dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague–Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6 mg kg−1 i.p.). Urine samples were collected prior and up to 72 h after treatment in animals that were ≥ 25 days old. Several serum, urinary and ‘omic’ injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age‐related Cis‐induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day‐old vs 10 ≥ 80 > 40 > 25‐day‐old rats, respectively. The increased levels of kidney injury molecule‐1 (Kim‐1: urinary protein/tissue mRNA) provided evidence of early Cis‐induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim‐1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi‐age rat model can be used to demonstrate different age‐related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers. Published in 2009 by John Wiley & Sons, Ltd.
Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi‐age rat model could be used for pre‐clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age‐dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis).
At the Product Quality Research Institute (PQRI) Workshop held last January 14–15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of ...nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for
in vitro
characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced
in vivo
and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.
Nanoparticles (NP) often interfere with the mechanism and interpretation of high throughput in vitro toxicity assays. This interference may occur at any time during the assay and spans most NP ...systems. This study reports on a specific type of gold NP assay interference, where unmodified gold NPs were able to traffic certain assay molecules that contained primary amines across the cell membrane resulting in false positive results for toxicity assays. The enhanced assay molecule permeability was eliminated when the gold NP surface was both sterically and chemically blocked by polyethylene glycol (PEG). The results support the growing consensus that appropriate controls and assay validation should occur prior to interpretation of results of assays using NP.
During the cooking of meats, several highly mutagenic heterocyclic amines (HCAs) are produced. Three HCAs, IQ, MeIQx, and PhIP have been under study for carcinogenicity in cynomolgus monkeys, and to ...date, IQ has been shown to be a potent hepatocarcinogen. Concomitantly, the metabolic processing of these HCAs has been examined. Metabolism studies show that the potent hepatocarcinogenicity of IQ is associated with the in vivo metabolic activation of IQ via N-hydroxylation and the formation of DNA adducts. In monkeys undergoing carcinogen bioassay with IQ, N-hydroxylation was confirmed by the presence of the N-hydroxy-N-glucuronide conjugate of IQ in urine. The N-hydroxylation of IQ appears to be carried out largely by hepatic CYP3A4 and/or CYP2C9/10, and not by CYP1A2, an isoform not expressed in liver of this species. Notably MeIQx is poorly activated in cynomolgus monkeys and lacks the potency of IQ to induce hepatocellular carcinoma after a 5-year dosing period. The poor activation of MeIQx appears to be due to the lack of constitutive expression of CYP1A2 and an inability of other cytochromes P450, such as CYP3A4 and CYP2C9/10, to N-hydroxylate the quinoxalines. MeIQx is detoxified in monkeys largely by conjugation with glucuronide at the N-1 position. Although the carcinogenicity of PhIP is not yet known, the metabolic data suggest that PhIP will be carcinogenic in this species. PhIP is metabolically activated in vivo in monkeys by N-hydroxylation, as discerned by the presence of the N-hydroxy-N-glucuronide conjugate in urine, bile, and plasma. PhIP also produces DNA adducts that are widely distributed in tissues. The results from these studies support the importance of N-hydroxylation in the carcinogenicity of HCAs in nonhuman primates and by analogy, the importance of this metabolic activation step in the possible carcinogenicity of dietary HCAs in humans.
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