Margin Of Safety Values Research Articles

A sustainable and innovative method to determine parabens in body creams for exposure and risk assessment

Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) are among the most widely used preservatives in cosmetics, drugs, and foods. These compounds have been associated with toxic effects due to the overuse of products with parabens in their formulation. The toxicity of parabens may be correlated to endocrine disruption, owing to their ability to mimic the actions of estradiol. In this paper, a simple, sustainable, robust, and innovative dispersive liquid-liquid microextraction (DLLME) technique was developed and employed to extract these xenobiotics from body cream samples, aiming to calculate the margin of safety (MoS) to assess the risk of exposure. The validated method presented suitable linearity (r > 0.99), lower limits of detection (ranging from 0.01 to 0.04 % w/w), and satisfactory precision and accuracy (ranging from 4.33 to 10.47, and from −14.25 to 13.85, respectively). Seven of the ten analysed samples presented paraben contents within the acceptable concentration according to European legislation. The MoS value obtained for PrP (37.58) suggested its reduced safety, indicating that PrP may significantly contribute to systemic exposure resulting from the use of personal care products.

Experimental study for inorganic and organic profiling of toy makeup products: Estimating the potential threat to child health

Inorganic elements are added to toys as impurities to give desired stability, brightness, flexibility, and color; however, these elements may cause numerous health issues after acute or chronic exposure. In this study, the inorganic profile of 14 elements (Al, As, Ba, Cd, Co, Cr, Cu, Hg, Mn, Ni, Se, Sb, Pb, and Zn) in 63 toy makeup products was identified by inductively coupled plasma-mass spectrometry after microwave acid digestion method. Additionally, organic allergen fragrance was investigated by gas chromatography-mass spectrometry. The systemic exposure dosage (SED), margin of safety (MoS), lifetime cancer risk (LCR), hazard quotient (HQ), and hazard indices were used to assess the safety evaluation. Then, 57 out of 63 samples (90.48%) exceeded the limits at least for one toxic element with descending order Ni > Cr > Co > Pb > Sb > Cd > As > Hg. The SED values were compared with tolerable daily intake values and remarkably differences were found for Al and Pb. The MoS values for 57.15% of samples exceeded the limit value for Al, As, Cd, Co, Hg, Mn, Sb, and Zn elements. The LCR values were observed at 100% (n = 63), 79.37% (n = 50), 85.71% (n = 54), 77.78% (n = 49), and 18.87% (n = 10) for Cr, Ni, As, Pb, and Cd, respectively. Also, the skin sensitization risks were obtained for Cr and Ni at 26.980% (n = 17) and 9.52% (n = 6), respectively. The HQ values for 80% of samples were found to be ≥ 1 at least for one parameter. The investigation of fragrance allergens in samples did not show any significant ingredients. As a result, toy makeup products marketed in local stores were found to be predominantly unsafe. Children should be protected from harmful chemicals by regular monitoring and strict measures.

Next generation risk assessment: an ab initio case study to assess the systemic safety of the cosmetic ingredient, benzyl salicylate, after dermal exposure.

We performed an ab initio next-generation risk assessment (NGRA) for a fragrance ingredient, benzyl salicylate (BSal), to demonstrate how cosmetic ingredients can be evaluated for systemic toxicity endpoints based on non-animal approaches. New approach methodologies (NAMs) used to predict the internal exposure included skin absorption assays, hepatocyte metabolism, and physiologically based pharmacokinetic (PBPK) modeling, and potential toxicodynamic effects were assessed using pharmacology profiling, ToxProfiler cell stress assay, transcriptomics in HepG2 and MCF-7 cells, ReproTracker developmental and reproductive toxicology (DART) assays, and cytotoxicity assays in human kidney cells. The outcome of the NGRA was compared to that of the traditional risk assessment approach based on animal data. The identification of the toxicologically critical entity was a critical step that directed the workflow and the selection of chemicals for PBPK modeling and testing in bioassays. The traditional risk assessment and NGRA identified salicylic acid (SA) as the "toxdriver." A deterministic PBPK model for a single-day application of 1.54g face cream containing 0.5% BSal estimated the Cmax for BSal (1nM) to be much lower than that of its major in vitro metabolite, SA (93.2nM). Therefore, SA was tested using toxicodynamics bioassays. The lowest points of departure (PoDs) were obtained from the toxicogenomics assays. The interpretation of these results by two companies and methods were similar (SA only results in significant gene deregulation in HepG2 cells), but PoD differed (213μM and 10.6µM). A probabilistic PBPK model for repeated applications of the face cream estimated the highest Cmax of SA to be 630nM. The resulting margins of internal exposure (MoIE) using the PoDs were 338 and 16, which were more conservative than those derived from external exposure and in vivo PoDs (margin of safety values were 9,705). In conclusion, both traditional and ab initio NGRA approaches concluded that the daily application of BSal in a cosmetic leave-on face cream at 0.5% is safe for humans. The processing and interpretation of toxicogenomics data can lead to different PoDs, which can subsequently affect the calculation of the MoIE. This case study supports the use of NAMs in a tiered NGRA ab initio approach.

Characteristic and health risk of per- and polyfluoroalkyl substances from cosmetics via dermal exposure

In this work, 45 cosmetic samples were collected from China, and 27 target per- and polyfluoroalkyl substances (PFAS) were analyzed by ultrahigh-performance liquid chromatography-high resolution mass spectrometry. PFAS were found in all samples, including the products marketed for pregnant women, and the total concentrations of PFAS measured in each sample were in the range of 4.05 – 94.9 ng/g. Short-chain perfluorinated carboxylic acids were the dominant compounds contributing to over 60% of the total content. Perfluorobutanoic acid, with high placental transfer efficiency, was the major PFAS in cosmetics for pregnant women. Three emerging PFAS, 2-perfluorohexyl ethanoic acid, 3-perfluoropentyl propanoic acid (5:3) and perfluoro-2-propoxypropanoic acid, were also identified in the cosmetic samples at quantifiable levels. Significantly, positive correlations between individual PFAS were observed, indicating that there may be a common source for PFAS in these samples. Statistical analyses suggested that using plastic containers and precursor substances may be potential sources of PFAS in terminal products, and product aging may increase PFAS levels. From the PFAS analysis of the cosmetics, the margin of safety (MoS) and hazard quotient (HQ) were calculated to assess human health risks through dermal exposure by using these products. Although the MoS and HQ values obtained were deemed acceptable, the cumulative effect caused by composite and long-term exposure to these contaminants needs to be given greater attention by health authorities.

Quantitative Risk Assessment of Dermal Sensitization Potential Following Use of Shampoo Products Containing the Formaldehyde Releasing Preservative DMDM Hydantoin.

Historically, formaldehyde was used as a preservative in personal care products to extend product shelf-life; however, given its skin sensitization potential it has been phased out of use and replaced with formaldehyde-releasing preservatives, such as Dimethyloldimethyl hydantoin (DMDMH). A relationship has been established between positive patch test results following exposure to DMDMH and previous sensitization to formaldehyde. Upon direct contact with the skin, formaldehyde can react with skin proteins and cause an acute inflammatory reaction, which may progress to skin sensitization following repeated exposure. This quantitative risk assessment (QRA) aimed to assess the risk of skin sensitization induction following use of shampoo products containing the maximum allowable concentrations of DMDMH in formulation (1% w/v), translating to a free formaldehyde concentration of 0.02%. To determine a margin of safety (MOS) for exposure to DMDMH from use of shampoo products, consumer exposure levels (CEL) were estimated based on typical use scenarios and then benchmarked against an acceptable exposure level (AEL). The AEL was derived using a weight of evidence approach where a range of no expected sensitization induction levels (NESILs) was utilized. The MOS values for a shampoo product containing 1% DMDMH (.02% formaldehyde) was above 1 for the typical use scenario indicating a low likelihood of skin sensitization induction among healthy individuals. Thus, it can be concluded that shampoo products containing DMDMH at or below current allowable concentrations are not expected to increase the risk of skin sensitization induction.

Dispersive liquid-liquid microextraction and Monte Carlo simulation of margin of safety for octocrylene, EHMC, 2ES, and homosalate in sunscreens.

Dispersive liquid-liquid microextraction (DLLME) using a floating organic drop has been optimized and used for the sample preparation of four commonly used ultraviolet filter (UVF) substances in sunscreens. Plackett-Burman experimental design was used to screen 10 variables in DLLME. The most significant variables were then optimized by using a response surface method with a Box-Behnken design. DLLME followed by an optimized HPLC identified octocrylene, 2-ethylhexyl-4-methoxycinnamate, ethylhexyl salicylate, and homosalate as the frequently found UVFs in commercial sunscreens. The systemic exposure dosage and margin of safety (MoS) for the identified UVFs were estimated using in-use concentrations and application patterns. The average systemic exposure dosage values for octocrylene, 2-ethylhexyl-4-methoxycinnamate, ethylhexyl salicylate, and homosalate were 0.52, 0.61, 0.020, and 0.079 mg/kg body weight per day, respectively. Whereas the average MoS values for individual UVFs ranging from 296 to 3160 were all significantly higher than the limit value of 100, the combined exposure risks were slightly above the limit. The probabilistic health risk assessment using Monte Carlo simulation revealed that the combined MoS values were (mean, 10‰, 90‰) 342, 119, and 441, respectively. Regarding the usage of sunscreen cosmetics containing the UVFs studied, these results indicate a safety concern for those who apply multiple UVF products.

Risk assessment of trace metals in sunblock creams using DABCOnium-based ionic liquid-functionalized magnetic nanoparticles.

In the present study, we synthesized DABCOnium-based-Brønsted acidic ionic liquid-functionalized magnetic nanoparticles (Fe3O4@(SU-DBC) NPs). Their structure was characterized using various morphological and physicochemical techniques such as SEM, powder-XRD, XPS, FTIR, VSM, and BET. The Fe3O4@(SU-DBC) NPs have remarkable magnetic recovery, extensive colloidal stability, and excellent recyclability. The fabricated ionic liquid-modified magnetic NPs show capability for magnetic dispersive micro-solid-phase extraction (MD-μ-SPE) of trace metals (Cd, Cr, Ni, and Pb) from sunblock cream samples. Micro-sampling flame atomic absorption spectrometry (MS-FAAS) was used to analyze the analytes. For evaluating the simultaneous effects of various parameters on the extraction efficiency, a central composite design was employed. In the method validation, the recoveries ranged from 97.84 to 102.36%, with relative standard deviations of 0.97% to 3.27%. The detection limits of the proposed method ranged between 0.067 and 0.715 μg kg-1. The developed method showed high sensitivity and precision, and stable recovery. Health risks were evaluated using the margin of safety (MoS), hazard quotient (HQ), hazard index (HI), and lifetime cancer risk (LCR). Sunblock creams' MoS, HQ, and HI values were within permissible ranges, but LCR values were higher than permitted.

The 2-Methoxymethyl Modification of p-Phenylenediamine Reduces the Sensitization Risk for Hairdressers to Hair Dyes—An Occupational Hand Exposure–Based Risk Assessment

BackgroundAllergic contact dermatitis involving the hands is a common occupational skin disease for hairdressers and the potent sensitizers p-phenylenediamine (PPD) and toluene-2,5-diamine (PTD) are associated with the development of occupational allergic contact dermatitis.ObjectiveThe aim of the study was to analyze whether the use of the moderate sensitizer 2-methoxymethyl-PPD (ME-PPD) in professional hair dyes is a suitable tool to reduce the occupational contact allergy risk for hairdressers.MethodsHand exposure of hairdressers (N = 11) to ME-PPD was analyzed under routine hair coloring conditions in commercial salons. By accounting for wet work and uneven hand exposure, the daily hand exposure was derived and compared with the occupational acceptable exposure level (AEL), that is, the sensitization induction threshold of ME-PPD adjusted for interindividual variability among workers.ResultsThe daily hand exposure to ME-PPD was 1.6 μg/cm2, and the occupational AEL was 215 μg/cm2. The ratio of hand exposure to AEL was calculated as the margin of safety (MOS) against occupational sensitization. For ME-PPD, the MOS of 134 indicates a low likelihood of sensitization versus PPD and PTD with MOS values of 2.7 and 5.9, respectively.ConclusionsOur data predict that the use of ME-PPD in professional hair color products improves the protection of hairdressers against hair dye–related contact allergy versus the use of PPD and PTD.

In vitro–in silico-based prediction of inter-individual and inter-ethnic variations in the dose-dependent cardiotoxicity of R- and S-methadone in humans

New approach methodologies predicting human cardiotoxicity are of interest to support or even replace in vivo-based drug safety testing. The present study presents an in vitro–in silico approach to predict the effect of inter-individual and inter-ethnic kinetic variations in the cardiotoxicity of R- and S-methadone in the Caucasian and the Chinese population. In vitro cardiotoxicity data, and metabolic data obtained from two approaches, using either individual human liver microsomes or recombinant cytochrome P450 enzymes (rCYPs), were integrated with physiologically based kinetic (PBK) models and Monte Carlo simulations to predict inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. Chemical specific adjustment factors were defined and used to derive dose–response curves for the sensitive individuals. Our simulations indicated that Chinese are more sensitive towards methadone-induced cardiotoxicity with Margin of Safety values being generally two-fold lower than those for Caucasians for both methadone enantiomers. Individual PBK models using microsomes and PBK models using rCYPs combined with Monte Carlo simulations predicted similar inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. The present study illustrates how inter-individual and inter-ethnic variations in cardiotoxicity can be predicted by combining in vitro toxicity and metabolic data, PBK modelling and Monte Carlo simulations. The novel methodology can be used to enhance cardiac safety evaluations and risk assessment of chemicals.

ANALISIS PROFITABILITAS DAN NILAI TAMBAH USAHA INDUSTRI PANGAN PRODUK CARANG MAS DI KABUPATEN MAGETAN

Carang mas is a type of snack made from sweet potato. This study aims to determine the cost structure, the profitability and added value of processing sweet potatoes into carang mas by using descriptive and analytical methods. The location is chosen by applying purposive sampling, and sample is selected by census method. Data collection techniques used observation, interview, and note-taking. Data analysis methods used: (1) Cost; (2) Revenue; (3) Break event Point; (4) Profitability; and (5) Added Value. The results showed that the average variable cost is IDR 32.090.664,88 production/month and the average fixed cost is IDR 436.482,42 production/month. The average total cost spent is IDR 32,527,147.30 productions/month. The average revenue of the machete industry is IDR 39.486.431,28 production/month. The amount of Break Event Point units is 627,42 packages per month, while the of Break Event Point sales is IDR 2.330.414,69 production/month. The Margin Of Safety value is 94,10% and the value of the Marginal Income Ratio is 18,73%, so the profitability value in the business of carang mas is 17,62%. Processing of potato into carang mas generates the gross added value of IDR 1.400,75 per kilogram, while the net value added amounts to IDR 1.169,80 per kilogram. The average labor used in its industry is five people.

Determination of Toxic Elements in Facial Cosmetics from the Romanian Market and Their Health Risk Assessment

Nowadays, the growing demand for cosmetics is also associated with increased vulnerability to carcinogenic effects resulting from long-term exposure. In this work, toxic effects of trace elements and heavy metals (Cr, Co, Ni, Cu, As, Pb, Hg, and Cd) were investigated in facial cosmetic lipstick and eye shadow availalbe on the Romanian market by inductively coupled plasma – mass spectrometry (ICP-MS). The risk evaluation for human health was assessed using the systemic exposure dosage (SED) and the margin of safety (MoS). Our results show that the lead exceeded the acceptable safe manufacturing practice of 20 mg/kg in several samples, indicating an existing risk for consumers. The nickel, often associated with skin dermatitis and allergic reaction, had higher values than the 5 mg/kg recommended maximum weight. The highest heavy metals concentrations were in the eye shadow samples. The systemic exposure dosage and margin of safety values were within acceptable limits, and irrespective of this aspect, daily exposure can cause cumulative side effects, which is why a continuous monitoring of heavy metals adulteration needs to be performed.

ANALISIS FINANSIAL DENGAN PENDEKATAN COST VOLUME PROFIT PADA USAHA KOPI BUBUK BUKIT BARISAN DI KABUPATEN BENGKULU TENGAH

The purpose of this study is to estimate the amount of Bukit Barisan Coffee's operating profit that is reflected in the contribution margin, breakeven point, margin of safety (MOS), degree of operating laverage (DOL) and calculate profit target in next period. The research method used is a case study. The analysis used is cost-volume-profit analysis (CVP). The data used are primary and secondary data. Based on the results of the analysis, it was found that the profit was IDR 18,323,806 / month with a production of 896 kg / month, a contribution margin of IDR 21,028,250, a break even point of IDR 6,630,105 and 115 kg of ground coffee, a MOS value of IDR 44,921,895 and a DOL value of IDR 1.15. The planned profit target of IDR 20,156,186 can be achieved if sell 974 kg of coffee or get sales of IDR 55,757,635. To achieve the profit target, an alternative scenario is used to increase sales volume by 10% and a fixed selling price.

Effect Modeling Quantifies the Difference Between the Toxicity of Average Pesticide Concentrations and Time-Variable Exposures from Water Quality Monitoring.

Synthetic chemicals are frequently detected in water bodies, and their concentrations vary over time. Water monitoring programs typically employ either a sequence of grab samples or continuous sampling, followed by chemical analysis. Continuous time-proportional sampling yields the time-weighted average concentration, which is taken as proxy for the real, time-variable exposure. However, we do not know how much the toxicity of the average concentration differs from the toxicity of the corresponding fluctuating exposure profile. We used toxicokinetic-toxicodynamic models (invertebrates, fish) and population growth models (algae, duckweed) to calculate the margin of safety in moving time windows across measured aquatic concentration time series (7 pesticides) in 5 streams. A longer sampling period (14 d) for time-proportional sampling leads to more deviations from the real chemical stress than shorter sampling durations (3 d). The associated error is a factor of 4 or less in the margin of safety value toward underestimating and an error of factor 9 toward overestimating chemical stress in the most toxic time windows. Under- and overestimations occur with approximate equal frequency and are very small compared with the overall variation, which ranged from 0.027 to 2.4 × 1010 (margin of safety values). We conclude that continuous, time-proportional sampling for a period of 3 and 14 d for acute and chronic assessment, respectively, yields sufficiently accurate average concentrations to assess ecotoxicological effects. Environ Toxicol Chem 2020;39:2158-2168. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

PROSPEK SAHAM PERBANKAN DI INDONESIA

The focus of this research is to determine stocks provide the highest profit (gain opportunity) for investors. Investors will compare opportunities in choosing investment in the banking sector by comparing the combination of long-term growth rates rather than bank fundamentals with stock valuations. The population in this study is banking stocks included in the LQ45 index. The method of data collection uses a sample survey with a purposive sampling technique with the criteria of banking stocks with the largest market capitalization and has a high level of liquidity in trading values, and has consistently been included in the LQ45 index for the last 10 years (2008 to 2017). The number of samples selected were 4 banks consisting of Bank Mandiri (BMRI), Bank BRI (BBRI), Bank BCA (BBCA), and Bank BNI (BBNI). Data collection techniques through documentation, as well as quantitative data sourced from secondary data. Data analysis techniques by comparing the growth of fundamental performance such as Return On Assets (ROA), Return On Equity (ROE), Debt to Equity (DER), Capital Addequacy Ratio (CAR), and Non Performing Loans (NPL). Whereas market performance through Share Price, Earning Per Share (EPS), Price Earning Ratio (PER), Price to Earning Growth (PEG), and Dividend Yield by using compounded annual growth rate (CAGR). Then compare the value of the Margin Of Safety (MOS) Average in stock valuation analysis. The results of this study indicate that the financial performance of Bank BCA (BBCA) is superior to other banks according to DER, CAR and NPL. BRI is the best bank in generating profitability (ROA and ROE) compared to 3 other banks. Meanwhile, according to the stock market performance based on the order of the greatest opportunity level, Bank BNI has the best prospects because it has the largest EPS growth, the lowest stock price valuation, and sufficient MOS value, then ranked below it respectively are Bank Mandiri, Bank BRI, and Bank BCA .Keywords:Financial performance, market performance, and stock value

Evaluation of heavy metals in cosmetic products and their health risk assessment

Heavy metals’ contamination in cosmetic products is a serious threat. Present study was conducted to evaluate the concentrations of heavy metals (HMs) in various brands of cosmetic products with special emphasis on their health risk assessment. Five heavy metals including Cd, Cr, Fe, Ni and Pb were quantified in different brands of lotions, foundations, whitening creams, lipsticks, hair dyes and sunblock creams using atomic absorption spectrometry. Risk to the consumer’s health was determined using systemic exposure dosage (SED), margin of safety (MoS), hazard quotient (HQ), hazard index (HI) and lifetime cancer risk (LCR).On comparative basis, different brands of sunblock creams depicted highest concentration of Ni, Pb and Cr (7.99 ± 0.36, 6.37 ± 0.05 and 0.43 ± 0.01 mg/kg, respectively), whereas lipsticks had elevated levels of Fe at 12.0 ± 1.8 mg/kg, and Cd was maximum in lotions (0.26 ± 0.02 mg/kg). Multivariate analysis revealed strong associations among Cr, Ni and Pb, while Cd and Fe showed disparity in distribution and sources of contamination. MoS, HQ and HI values were within the permissible limit apart from for lotions and sunblock creams, while LCR value was higher than the permissible limit in all cosmetic products except lipsticks. Regular use of these products can cause serious threat to human health, particularly skin cancer on long time exposure. Therefore, continuous monitoring of cosmetic products, particularly with reference to HMs adulteration should be adopted to ensure the human safety and security.

Risk of dermal and inhalation exposure to chlorantraniliprole assessed by using whole-body dosimetry in Korea.

We determined the characteristics and evaluated associated risks of sprayed pesticide exposure among workers cultivating Korean cabbage. The test pesticide, a mixture of 3% chlorantraniliprole and 4% indoxacarb wettable granules diluted 2000 times, was sprayed on Korean cabbage within a 3000 m2 area in Goesan, Korea. Dermal exposures were measured using a whole-body dosimetry method. Exposure to chlorantraniliprole was observed among ten individuals, ranging from 140.4 to 4234.0µg person-1 . The legs were the most prominent exposure area (86.35%), with the face being the least exposed (0.06%). Exposure risk was assessed by calculating the margin of safety (MOS) on the exposure amount for each body part. The MOS based on dermal and inhalation exposure doses ranged from 59 to 1765. Exposure was the greatest for the legs, probably as a result of the low height of the crop and the use of a long-wand sprayer. An MOS value >1 indicates a low risk for applicators using this method of application. However, with tall crops, exposure level and MOS values can vary widely, as MOS increases or decreases based on exposure dose. Therefore, future research is needed to better understand appropriate safety precautions when working with potent pesticides. © 2018 Society of Chemical Industry.

Risk of human exposure to metals in some household hygienic products in Nigeria.

This study presents data on the levels and risk of human exposure to Cd, Pb, Cr, Ni, Cu, Co, Mn, Zn and Fe in some popular brands of household hygienic products (HHPs) available in Nigeria. The HHPs were digested with a mixture of HNO3, HCl and HClO4 in a ratio of 1:3:1 and the concentrations of the selected metals were quantified by atomic absorption spectrophotometry. The metal concentrations (in μg g-1) in these products ranged from 0.4 to 5.4, <0.09-47.0, <0.12-43.7, <0.06-7.5, <0.12-9.5, <0.06-15.0, <0.09-24.5, 9.0-675 and 62.4-434 for Cd, Pb, Cr, Cu, Co, Ni, Mn, Zn and Fe respectively. The systemic exposure dosages for the metals, arising from the use of these HPPs, were less than their respective provisional tolerable daily intake/recommended dietary allowance values. The household hygienic products are safe to use by humans based on the margin of safety values that were all above 100. However, the products contained significant levels of toxic (Cd and Pb), allergenic (Ni and Cr) and other low toxicity metals (Mn, Zn and Fe), which could be a potential threat to the environment.

Hexavalent chromium in tattoo inks: Dermal exposure and systemic risk.

The presence of hexavalent chromium (Cr[VI]), which is carcinogenic to humans and a dermal sensitizer, in tattoo inks may represent a serious health concern. The level of this impurity is limited to 0.2 mg/kg in tattoo inks by the European Resolution ResAP(2008)1. To analyse 29 tattoo inks, produced in Europe and the United States, of different colours and brands, for Cr(VI) to assess their conformity with ResAP(2008)1 and to characterize dermal and systemic risks. Ion chromatography and inductively coupled plasma mass spectrometry were used to determine the levels of Cr(VI) in inks; risk characterization was performed by calculating the systemic exposure dosage (SED) and margin of safety (MoS). Ninety per cent of inks contained Cr(VI) (range: 0.22-4.09 mg/kg), ie, above the maximum allowed level, and no information appeared on the label. More than 1 mg/kg Cr(VI) was detected in 27.6% of inks; these might represent a possible cause of dermal adverse reactions. Exposure to Cr(VI) in inks resulted in negligible SED values and MoS values of >100 (safety threshold), indicating no appreciable systemic risk. The minimization of Cr(VI) contamination and the use of technology compliant with good manufacturing practices is recommended to increase the safety of tattoo inks.

Risk assessment of N-nitrosodiethylamine (NDEA) and N-nitrosodiethanolamine (NDELA) in cosmetics

ABSTRACTN-nitrosamines and their precursors found in cosmetics may be carcinogenic in humans. Thus the aim of this study was to carry out risk assessment for N-nitrosamines (N-nitrosodiethanolamine [NDELA], N-nitrosodiethylamine [NDEA]) and amines (triethanolamine [TEA], diethanolamine [DEA]) levels in cosmetics determined using validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) procedures. NDELA and NDEA concentrations were present at levels of “not detected” (N.D.) to 596.5 μg/kg and N.D. to 40.9 μg/kg, respectively. TEA and DEA concentrations ranged from N.D. to 860 μg/kg and N.D. to 26.22 μg/kg, respectively. The nitrite concentration (3–2250 mg/l), number of nitrosating agents to a maximum 5, and pH (3.93–10.09) were also assessed. The impact of N-nitrosamine formation on the levels of TEA, DEA, nitrite, and other nitrosating agents was also examined. N-nitrosamine concentrations correlated with the number of nitrosating agents and nitrite concentrations. Data demonstrated that higher nitrite concentrations and a greater number of nitrosating agents increased NDELA and NDEA yields. Further, the presence of TEA and DEA exerted a significant influence on N-nitrosamine formation. Risk assessments, including the margin of exposure (MOE) and lifetime cancer risk (LCR) for N-nitrosamines and margin of safety (MOS) for amines, were calculated using product type, use pattern, and concentrations. Exposure to maximum amounts of NDELA and NDEA resulted in MOE > 10,000 (based upon the benchmark dose lower confidence limit 10%) and LCR <1 × 10−5, respectively. In addition, TEA and DEA concentrations in cosmetic samples resulted in MOS values >100. Therefore, no apparent safety concerns were associated with cosmetic products containing NDELA, NDEA, TEA, and DEA in this study. However, since amines and nitrosating agents produce carcinogenic nitrosamines, their use in cosmetics needs to be minimized to levels as low as technically feasible.

In Vitro Evaluation of Sunscreen Safety: Effects of the Vehicle and Repeated Applications on Skin Permeation from Topical Formulations.

The evaluation of UV-filter in vitro percutaneous absorption allows the estimation of the systemic exposure dose (SED) and the margin of safety (MoS) of sunscreen products. As both the vehicle and pattern of application may affect sunscreen safety and efficacy, we evaluated in vitro release and skin permeation of two widely used UV-filters, octylmethoxycinnamate (OMC) and butylmethoxydibenzoylmethane (BMBM) from topical formulations with different features (oil in water (O/W) emulsions with different viscosity, water in oil (W/O) emulsion, oils with different lipophilicity). To mimic in-use conditions, we carried out experiments repeating sunscreen application on the skin surface for three consecutive days. BMBM release from all these vehicles was very low, thus leading to poor skin permeation. The vehicle composition significantly affected OMC release and skin permeation, and slight increases of OMC permeation were observed after repeated applications. From skin permeation data, SED and MoS values of BMBM and OMC were calculated for all the investigated formulations after a single application and repeated applications. While MoS values of BMBM were always well beyond the accepted safety limit, the safety of sunscreen formulations containing OMC may depend on the vehicle composition and the application pattern.