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.     

Assessment of the phototoxic potential of cosmetic products.

The cosmetics are nontoxic or less toxic in perse but photoactivation may then sensitize and could produce additional phototoxicity. Phototoxicity assessment of ten different lipsticks and eight facial creams was conducted. Results revealed that six lipsticks and five facial creams generated reactive oxygen species (ROS), produced haemolysis and caused lipid peroxidation in human erythrocytes (in vitro) under sunlight exposure. Seven creams and one lipstick were alkaline while one cream and two lipsticks were acidic. The test lipsticks and creams showed absorption in UV/visible range. The study demonstrated synergistic action of cosmetic products and sunlight. Therefore, sunlight exposure should be avoided after the use of photosensitive cosmetics.     

DDTC-APDC-MIBK-正己烷络合萃取测定化妆品中的铅和镉

目的建立火焰原子吸收分光光度法测定化妆品中铅、镉。方法湿法消解样品后,应用DDTC-APDC络合铅、镉,经M IBK-正己烷萃取进一步浓缩,采用空气-乙炔火焰原子吸收分光光度法测定铅、镉的含量。结果化妆品中铅、镉的萃取回收率分别为99.6%~104%、91.4%~98.9%,仪器精密度(RSD)分别为1.4%、1.4%,方法精密度(RSD)分别为1.9%、1.8%。结论该方法可准确检出一些化妆品中基底干扰大、金属含量低于仪器检出限的样品。     

Acute effects of lead on renal electrolyte excretion and plasma renin activity

Since lead accumulates in the kidney and interferes with the renal transport of amino acids and glucose, we tested the hypothesis that acute doses of lead also reduce tubular electrolyte reabsorption and alter the secretion of renin. In sodium pentobarbital-anesthetized dogs, acute iv lead increased the excretion of sodium, potassium, calcium, and water, despite a constant glomerular filtration rate; therefore lead reduced the tubular reabsorption of these substances. Lead also caused an increase in plasma renin activity. The threshold dose of acutely administered lead necessary to elicit these responses was determined in dose-response experiments on unanesthetized rats; a dose of 0.1 mg of lead/kg was sufficient to cause significant increases in plasma renin and the renal excretion of sodium. Lead concentrations in the tissues of the rats were measured in samples taken immediately at the conclusion of the study; the threshold dose of lead was associated with very low blood lead (< 5 μg/100 ml) and kidney lead (1.2 μg/g wet wt). These effects of lead are discussed with regard to their possible clinical significance.     

Human health risk of polychlorinated biphenyls and organochlorine pesticides resulting from seafood consumption in South Korea, 2005–2007

Organochlorines (OCs) such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), were measured in 26 species of seafood commonly consumed by the Korean population. PCBs and DDTs were the predominant contaminants with concentrations from 0.2 to 41 ng/g wet wt and from < 0.04 to 37 ng/g wet wt, while CHLs (<0.01–1.9 ng/g wet wt), HCB (<0.004–1.0 ng/g wet wt), and HCHs (<0.02–0.4 ng/g wet wt) were 1–2 orders of magnitude lower than the concentrations of PCBs and DDTs. The dominant PCBs and OCPs were PCB 153, 187, 138, and 118 and p,p′-DDE, HCB, p,p′-DDT, and p,p′-DDD, respectively. Dietary intakes of OCs for the general population, males, and females were estimated as 69, 78, and 60 ng/kg body weight/week, respectively. Mackerel, tuna, and hairtail were the main contributors to the dietary intakes of OCs. Among the eight age groups investigated, infants <2 years had the highest dietary exposure to OCs. Hazard ratios of non-cancer risk of all of the OCs were less than one, while the lifetime cancer risks of PCBs and DDTs were all greater than unity for Korean populations.     

Pharmaceutical evaluation of different shampoo brands in local Saudi market

Shampooing is the most common form of hair treatment. Shampoos are primarily products aimed at cleansing the hair and scalp. There are many brands of shampoos in Saudi Arabia, available from different sources, locally and imported from other countries. This study aims to investigate whether such brands comply with the Saudi standard specifications for shampoos, issued by the National Center for Specifications and Standards, and to what extent these specifications are applied. Six shampoo brands were randomly collected from Riyadh market (Pantene®, Sunsilk®, Herbal essences®, Garnier Ultra Doux®, Syoss® and L'Oreal Elvive®). The selected shampoos were evaluated according to their physicochemical properties, including organoleptic characterization, pH measurement, percentage of solid content, rheological measurements, dirt dispersion level, foaming ability and foam stability, and surface tension. All shampoos had a good percentage of solids, excellent foam formation with stable foam and a highly viscous nature. Regarding the pH measurement, all shampoo samples were within the specified range with good wetting ability.     

An observational study on adverse reactions of cosmetics: The need of practice the Cosmetovigilance system

IntroductionCosmetovigilance is public health surveillance on cosmetic products with a public health objective. Since the radical development in beautifying products in Saudi Arabia, the Saudi Food and Drug Authority takes the responsibility of regulating cosmetic products and issuing guidelines to ensure its safety. Despite this, there exists a lacuna of Re published reports on cosmetics-related adverse reactions in the Saudi population. We aimed to assess self-reported adverse reactions in the general public of the Eastern Province, Saudi Arabia.Materials and MethodA cross-sectional study was conducted for three months. The questionnaire for data collection was adopted and modified from previous studies for the cosmetic utilization behaviors and adverse reactions.ResultsAmong the 425 participants, 50.6% reported that they had at least one adverse reaction in the past two years. Redness of the skin (19%), pimples (15%), and itching (13%) were the commonly reported adverse reactions. The majority of the adverse reactions were reported with hair care (29%) and skincare products (25%). The majority [n = 181 (84.2%)] of the participants with managed the ARs by the cessation of the product use. The univariate analysis found that gender, age, allergic to medications and food, family history of allergy, mixing cosmetics, and frequent switching of cosmetic brands were associated with adverse events. However, the adjusted analysis found that allergic to medication (adjusted OR: 3.9), family history of allergy (adjusted OR: 1.91), and mixing cosmetics (adjusted OR: 1.70) were significantly associated with cosmetics-related adverse reactions.ConclusionCosmetovigilance is a model of safety monitoring of cosmetics. It can be considered as a one of the element in public health activities. Pharmacists should be more vigil on this issue in the near future. To strengthen the findings further, a national wide prevalence study can be conducted prospectively and analyses causality and report to the pharmacovigilanvce system of the country.     

Levels of organochlorine contaminants in organic and conventional cheeses and their impact on the health of consumers: An independent study in the Canary Islands (Spain)

In the present work we have evaluated the levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in 61 commercially available brands of cheese (54 conventional and 7 organic) to estimate their relevance as a source of organochlorines. Our results showed that hexachlorobenzene, α-HCH, dieldrin, p,p′-DDE, and PCBs 153 and 180 were present in most of the samples independent of the cheese type. The concentration of OCPs was low for both types of cheese, although organic had lower concentrations than conventional. The estimated daily intake (EDI) of OCPs was lower than the tolerable daily intake (TDI). The levels of PCBs in cheese were also low; however, there were higher levels of PCBs in organic than in conventional brands. Levels of dioxin- like PCBs (DL-PCBs) in both types of cheese reached concentrations in the 75th percentile higher than 3 pg WHO–TEQ/g fat, and above 100% of the levels established by the EU. People consuming the most contaminated brands could have an EDI well above the recommended TDI (2 pg WHO–TEQ/kg bw/day). These results are of concern as the adverse health effects exerted by dioxin-like compounds are well known.     

Acute and chronic effects of neonatal lead exposure on development of the visual evoked response in rats

Developmental electrophysiologic studies of the visual evoked response (VER) provided a means for evaluating the effects of lead on central nervous system (CNS) ontogeny. Newborn rats exposed to Pb via dams' milk (dams' consuming 0.2% lead acetate solution) on Days 1 through 21 exhibited no changes in growth rate, age of eye opening, or brain weights (wet and dry). At 21 days of age, the lead concentrations in blood and brain of controls were 6 ± 1 and 7 ± 1 μg/100 ml, respectively while rats treated with lead had 65 ± 9 and 53 ± 4 μg/100 ml, respectively. VERs were recorded on Days 9–13, 16, 20, and 100. Lead exposure produced a significant increase in the latency of the primary (P₁N₁) and the secondary (P₂N₂) components of the VER throughout the neonatal period. Significantly longer latencies were also seen in adult rats (Day 90) exposed to Pb only during suckling. Lead concentrations in blood and brain of adult controls were 5 ± 1 and 11 ± 1 μg/100 ml, respectively. Adult lead-treated rats had 7 ± 1 and 13 ± 2 μg/100 ml, respectively. Exposed adults also exhibited a significantly decreased CNS recoverability function, as indicated by an increased latency to paired flashes, and a significantly decreased ability to follow repetitive light flashes compared to controls.     

Profiling and quantification of isoflavone-C-glycosides impurities in puerarin injection by liquid chromatography coupled to ESI-ion trap mass spectrometry

An HPLC/DAD/MSⁿ method was established for the qualitative and quantitative analysis of the impurities in puerarin injection (PI), a widely used drug in China. The analytical HPLC was performed on an Agela RP-C18 column using 0.1% aqueous formic acid (v:v) and methanol as mobile phase. A total of nine impurities were detected and eight of them were identified as isoflavone-C-glycosides basing on their UV spectra and MSⁿ spectra and comparing with the literature data. An HPLC method for the assay of two common impurities in the commercial PI samples, i.e., neopuerarin A and neopuerarin B, was then established. The validation of the method, including sensitivity, linearity, precision, accuracy, was carried out. The calibration curves showed good linearity of R² > 0.9999 and LOQ (S/N = 10) were less than 3.73 ng. The precision was evaluated by intra- and inter-day assays and R.S.D. values were less than 0.94%. The average recovery rates were 97.0% and 99.5%, respectively, with R.S.D. less than 1.38%. The contents of neopuerarin A and neopuerarin B in various commercial brands of PI samples varied over the range of 0.30–1.16% and 0.42–1.66%, respectively. This is the first report on the impurities in PI.     

2012～2017年某检验机构化妆品行政许可检验数据分析

目的 了解国外进口化妆品和国内申请上市特殊用途化妆品的质量。方法 按《化妆品卫生规范》（2007年版）和《化妆品安全技术规范》（2015年版）及《化妆品行政许可检验规范》（2010年）对2012年至2017年企业委托检验的需行政审批的化妆品进行了检验,并对检验数据进行了统计分析。结果 进口行政许可检验化妆品主要来源于韩国和日本;国产特殊用途化妆品主要来自于海南和广东。不合格项目主要是毒理学试验（多皮）和微生物指标（菌落总数、霉菌和酵母菌总数）,主要为进口非特殊用途化妆品,大部分来自韩国和美国。结论 应加强对行政许可检验结果的统计分析,及时发现规律性、普遍性问题,有利于调整审评内容,必要时增加进口化妆品生产企业现场核查内容,以保障我国人民群众的化妆品使用安全。     

The chemical composition of smokeless tobacco: A survey of products sold in the United States in 2006 and 2007

Selected toxicant concentrations and other chemical measures have been determined for 43 U.S. smokeless tobacco products sold in 2006 and 2007. Products evaluated included moist snuff, dry snuff, loose leaf, plug, dissolvable and snus tobacco brands. Reference products available for scientific research purposes and eleven Swedish products were also evaluated and compared to the commercial products studied. Chemical endpoints determined included benzo[a]pyrene (B[a]P), N′-nitrosonornicotine (NNN), N′-nitrosoanatabine (NAT), N′-nitrosoanabasine (NAB), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-Nitrosodimethylamine (NDMA), nitrite, cadmium, lead, arsenic, nickel, chromium, chloride, water, pH and nicotine. Different toxicant profiles were observed for the products studied, with snus tobacco brands generally containing relatively low concentrations of B[a]P and tobacco specific nitrosamines (TSNAs) compared to other moist snuffs. Smokeless tobacco reference product toxicant profiles were similar to corresponding commercial products, with the exception of the TSNA content of the dry snuff reference material. TSNA concentrations observed for all commercial products were lower than historically reported values, likely reflecting changes in product shelf life, tobacco curing practices and, possibly, product blend formulations during the last 20–30 years. The survey results summarized provide a temporal point of comparison with future data anticipated from FDA “harmful and potentially harmful constituents in tobacco products” reporting.     

The essential and toxic elements in tissues of six commercial demersal fish from Eastern Mediterranean Sea

The essential elements and contaminants (Pb and Cd) were determined seasonally in the muscle and liver of six demersal fish species Sparus aurata, Chelidonichthys lucernus, Upeneus molluccensis, Solea solea, Merluccius merluccius and Saurida undosquamis from the ?skenderun Bay, Eastern Mediterranean Sea. The concentrations in muscles of fish species were 474–1534 mg/kg for Na, 574–3374 mg/kg for K, 72.7–496 m/kg Ca, 94.1–210 mg/kg for Mg. Muscle accumulated the lowest levels of elements. Trace element and contaminant levels in muscle were highest in the spring and winter. The Cu and Ni concentrations were highest in the winter. The Zn, Cr and Fe concentrations were highest in the spring. The maximum Pb concentrations in the muscle and liver of fish species was 0.58 and 0.89 mg/kg (wet wt) in the autumn. The maximum Cd concentration in the muscle and liver tissues of fish was 0.20 mg/kg and 0.63 mg/kg (wet wt) in the winter. The Cr, Pb, Cd, Cu and Zn levels in muscle were found to be lower than permissible limits. Estimated weekly and daily intake for Pb and Cd was far below the PTWI and PTDI values. The consumption of these species from this region is not problem on human health.     

Analytical control of process impurities in Pazopanib hydrochloride by impurity fate mapping

Understanding the origin and fate of organic impurities within the manufacturing process along with a good control strategy is an integral part of the quality control of drug substance. Following the underlying principles of quality by design (QbD), a systematic approach to analytical control of process impurities by impurity fate mapping (IFM) has been developed and applied to the investigation and control of impurities in the manufacturing process of Pazopanib hydrochloride, an anticancer drug approved recently by the U.S. FDA. This approach requires an aggressive chemical and analytical search for potential impurities in the starting materials, intermediates and drug substance, and experimental studies to track their fate through the manufacturing process in order to understand the process capability for rejecting such impurities. Comprehensive IFM can provide elements of control strategies for impurities. This paper highlights the critical roles that analytical sciences play in the IFM process and impurity control. The application of various analytical techniques (HPLC, LC–MS, NMR, etc.) and development of sensitive and selective methods for impurity detection, identification, separation and quantification are highlighted with illustrative examples. As an essential part of the entire control strategy for Pazopanib hydrochloride, analytical control of impurities with ‘meaningful’ specifications and the ‘right’ analytical methods is addressed. In particular, IFM provides scientific justification that can allow for control of process impurities up-stream at the starting materials or intermediates whenever possible.     

Heavy metal concentrations in diet and livers of Black-crowned Night Heron <Emphasis Type="Italic">Nycticorax nycticorax</Emphasis> and Grey Heron <Emphasis Type="Italic">Ardea cinerea</Emphasis> chicks from Pyeongtaek,Korea

This study presents concentrations of iron, manganese, zinc, copper, lead and cadmium in diet and livers of Black-crowned Night Heron Nycticorax nycticorax and Grey Heron Ardea cinerea chicks from Pyeongtaek, Gyeonggi-do, Korea. Heavy metal concentrations of heron chicks were not related to concentrations in the diet. Copper concentrations were significantly greater in the diet of Black-crowned Night Herons (geometric mean = 13.6 wet μg/g) than Grey Herons (7.45 wet μg/g), other metal concentrations did not differ between the diet of two species. Manganese (respectively 3.20 wet μg/g, 1.41 wet μg/g) and cadmium (respectively 13.4 wet μg/kg, 1.41 wet μg/kg) concentrations were higher in livers of Black-crowned Night Heron chicks than Grey Heron chicks, but zinc, iron, copper and lead concentrations in livers did not differ in between two herons. The essential elements were at background levels, however copper concentrations were relatively higher than previously reported from Korea. Lead and cadmium concentrations were within background levels for herons.     

Determination of acrylamide level in popular Iranian brands of potato and corn products

Acrylamide is a chemical found in starchy foods that have been cooked at high temperatures. These include crisps, chips, bread and crisp breads. It was first discovered by scientists in Sweden in 2002. The Objective of this study is to determine the level of acrylamide in popular Iranian brands of potato crisps and corn products, produced by domestic food industrial factories. For this reason 7 brands of potato and 8 brands of corn products (10 each) were collected, crashed and after preparing the extracts of each sample, using LC–MS–MS spectrometry for measuring acrylamide amount. Results showed that in different brands of potato and corn products there were different amounts (244–1688 μg/kg) and (<30–410 μg/kg) of acrylamide, respectively. As acrylamide is a dangerous toxin for human health, so it needs to reduce the level of acrylamide in these products that are used extensively by people specially children.     

Changes in correlation coefficients of exposure markers as a function of intensity of occupational exposure to toluene

This study was initiated to identify a marker of choice to monitor occupational exposure to toluene through quantitative evaluation of changes in correlation coefficients (CCs), taking advantage of a large database. Six known or proposed exposure markers in end-of-shift blood (B) and urine (U) were studied, i.e., toluene in blood (Tol-B) and benzyl alcohol, benzylmercapturic acid, o-cresol, hippuric acid and toluene in urine (BeOH-U, BMA-U, o-CR-U, HA-U, and Tol-U, respectively). To construct a database, data on 8-h time-weighted average intensity of occupational exposure to toluene and resulting levels of the six exposure markers in blood or urine were cited for 901 cases from previous four publications of this study group and combined with 146 new cases. In practice, 874 cases (all men) were available when extremely dilute or dense urine samples were excluded. The 874 cases were classified taking the upper limit (from 120 ppm to 1 ppm) of the toluene exposure concentration, and the CCs for the six markers with TWA toluene exposure intensity were calculated. For further evaluation, the 874 cases were divided into 10%-tiles in terms of TWA toluene exposures, and several 10%-tiles were combined so that sufficient numbers of cases were available for calculation of the CCs at various levels of toluene exposure. Perusal was made to know whether or not and which one of the six makers gave significant CC even at low level of toluene exposure. The CCs for BMA-U, o-CR-U and HA-U with TWA toluene exposure were well >0.7 when toluene exposure was intense (e.g., up to 60–100 ppm as the upper limit of the exposure range), but were reduced when the upper limit of toluene exposure was less than 50 ppm, and the CCs were as small as ≦0.2 when the upper limit was about 10 ppm or less. In contrast, Tol-U and Tol-B were correlated with exposure to toluene down to the ≦3 ppm range. The CC for BeOH-U was <0.1 almost throughout the exposure ranges. Further analyses showed that the CCs for all markers (except the CC for BeOH-U) were >0.4 when the cases in the 60th–100th%-tiles were examined. The CCs for Tol-U and Tol-B were >0.3 also for cases in the 0th–60th or 30th–70th%-tiles, whereas the CCs for other four markers were <0.3. In over-all evaluation, it was concluded that HA and o-CR are among the markers of choice to monitor occupational toluene exposure at high levels, and that only un-metabolized toluene in urine or in blood is recommended when toluene exposure level is low (e.g., 10 ppm or less). Toluene in urine may be preferred rather than that in blood due to practical reasons, such as non-invasiveness.     

Investigation of lead contents in lipsticks by solid sampling high resolution continuum source electrothermal atomic absorption spectrometry

In this study, the lead contents of different kinds of lipsticks were determined by solid sampling high resolution continuum source electrothermal atomic absorption spectrometry (SS-HR-CS ET AAS) and the results were compared with those obtained after microwave-assisted acid digestion of the samples. The experimental parameters for solid sampling such as the maximum amount of sample on the platforms of solid autosampler, graphite furnace program were optimized. Samples were directly loaded on the platforms of solid autosampler between 0.25 and 2.0 mg and lead was determined applying 800 °C for pyrolysis and 2100 °C for atomization. Under optimized conditions, interference-free determination could be performed using aqueous standards. The LOD and the characteristic mass were 21.3 and 12.6 pg, respectively. The lead in the same lipstick samples was determined after microwave-assisted acid digestion and compared with those found by solid sampling. Mostly, there was no significant difference between the lead concentrations found by the two techniques. The lead in 25 lipstick samples with different properties were 0.11–4.48 ng mg^?1 which were not significantly different from those (<0.026–7.19 ng mg^?1) reported by FDA for around 400 samples.     

Ascorbic acid supplementation does not improve efficacy of meso-dimercaptosuccinic acid treatment in lead-exposed suckling rats

It was suggested that ascorbic acid as a natural chelating agent can influence lead toxicokinetics and improve chelating properties of dimercaptosuccinic acid (DMSA) in adult rats. In this paper potential benefits of ascorbic acid supplementation, alone or combined with DMSA, in decreasing lead retention in suckling rats were evaluated. Such data in young mammals are not available. L-Ascorbic acid (daily dose 650 mg/kg b.wt.) and/or DMSA (daily dose 91 mg/kg b.wt.) were administered orally to suckling Wistar rats either during ongoing 8-day oral lead exposure (as acetate; daily dose 2 mg lead/kg b.wt.) or after 3-day lead exposure (total dose 12 mg lead/kg b.wt.). Lead concentrations were analysed in the carcass (skeleton), liver, kidneys and brain by atomic absorption spectrometry. By ascorbic acid supplementation lead retention was not reduced under either lead exposure condition. Lead concentration was even increased in the carcass. Treatment with DMSA under both exposure conditions significantly reduced lead in all analysed tissues. Combined treatment with ascorbic acid and DMSA during ongoing lead exposure was substantially less effective than DMSA treatment alone, and did not affect DMSA efficacy when administered after lead exposure. It was concluded that ascorbic acid administered either during or after lead exposure in suckling rats has no beneficial effect on either lead retention or DMSA chelation effectiveness.     

Lead in blood and tissues of mice after administration of low lead doses

Lead levels in whole blood could be determined reliably up to a lower limit of 2 g/100 ml blood, using a modified micromethod of the graphite tube furnace technique. Lead contents of various tissues were also determined by using the automated graphite tube furnace after wet ashing of the organs with nitric acid in autoclaves.Animal experiments with mice showed no measurable increase in blood lead level after a single, 10- or 30-days oral administration of lead in doses of 10–1000 g lead acetate/kg body weight/day. However, these doses led to a rise in tissue lead content. There was a clear dependence of tissue lead content on type of organ examined, lead dose and duration of lead exposure.According to our experiments, the threshold dose which leads to a long-term increase in tissue lead content is assumed to be about 100 g lead acetate/kg body weight/day, orally administered.We are thankful to Prof. Dr. H. Rüssel, Hannover and Dr. M. Fleischer, Saarbrücken for helping in comparison studies.We would also like to thank Mr. H. Dick and Miss. Ch. Hecker for the technical and laboratory assistance.