ArticleLiterature Review

Evaluation of the health aspects of methyl paraben: A review of the published literature

Authors:
  • Burdock Group
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Abstract

Methyl paraben (CAS No. 99-76-3) is a methyl ester of p-hydroxybenzoic acid. It is a stable, non-volatile compound used as an antimicrobial preservative in foods, drugs and cosmetics for over 50 years. Methyl paraben is readily and completely absorbed through the skin and from the gastrointestinal tract. It is hydrolyzed to p-hydroxybenzoic acid, conjugated, and the conjugates are rapidly excreted in the urine. There is no evidence of accumulation. Acute toxicity studies in animals indicate that methyl paraben is practically non-toxic by both oral and parenteral routes. In a population with normal skin, methyl paraben is practically non-irritating and non-sensitizing. In chronic administration studies, no-observed-effect levels (NOEL) as high as 1050 mg/kg have been reported and a no-observed-adverse-effect level (NOAEL) in the rat of 5700 mg/kg is posited. Methyl paraben is not carcinogenic or mutagenic. It is not teratogenic or embryotoxic and is negative in the uterotrophic assay. The mechanism of cytotoxic action of parabens may be linked to mitochondrial failure dependent on induction of membrane permeability transition accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation. Parabens are reported to cause contact dermatitis reactions in some individuals on cutaneous exposure. Parabens have been implicated in numerous cases of contact sensitivity associated with cutaneous exposure; however, the mechanism of this sensitivity is unknown. Sensitization has occurred when medications containing parabens have been applied to damaged or broken skin. Allergic reactions to ingested parabens have been reported, although rigorous evidence of the allergenicity of ingested paraben is lacking.

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... Additionally, the low frequency of sensitization, their water solubility which is sufficient to produce solutions, inertness, the fact they do not change consistency or coloration of products and their nonperceptible odor or taste are properties which make parabens interesting compounds [20]. In parabens, an increase in alkyl chain length improves antimicrobial effectiveness, but the water solubility decreases, as can be seen in the Table 1 [21]. ...
... Parabens are more efficient as preservatives against fungi than bacteria, and, regarding the action against bacteria, they are more efficient against Gram-positive than Gramnegative bacteria. Their range of effectiveness may be wider when used as a combination of different parabens [21]. Additionally, they are effective at neutral and acid pH, and alkaline solutions until pH = 8, where their preservative functions start to decrease [22]. ...
... Propylparaben is nonirritating and nonsensitizing for normal skin populations, but sensitizing effects were detected in the application of medicines that contained parabens for damaged or broken skin [22]. The Ophthalmic Drug Panel of the United States Food and Drugs Administration's Bureau of Drugs considered MP and PP unsuitable for use in ophthalmic solutions preparations because they can cause eye irritation [21]. ...
Article
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Parabens are widely used in different industries as preservatives and antimicrobial compounds. The evolution of analytical techniques allowed the detection of these compounds in different sources at µg/L and ng/L. Until today, parabens were already found in water sources, air, soil and even in human tissues. The impact of parabens in humans, animals and in ecosystems are a matter of discussion within the scientific community, but it is proven that parabens can act as endocrine disruptors, and some reports suggest that they are carcinogenic compounds. The presence of parabens in ecosystems is mainly related to wastewater discharges. This work gives an overview about the paraben problem, starting with their characteristics and applications. Moreover, the dangers related to their usage were addressed through the evaluation of toxicological studies over different species as well as of humans. Considering this, paraben detection in different water sources, wastewater treatment plants, humans and animals was analyzed based on literature results. A review of European legislation regarding parabens was also performed, presenting some considerations for the use of parabens.
... The parabens are among the most useful drug preservatives. For the first time they have been used at the middle of twenty years of the last century as drug preservatives in the production of suppositories, syrups, injectable solutions, eye drops and contraceptive products [12]. ...
... In nature, methyl paraben naturally occurs in wild blackberry, about 0.15 ppm, in papaya juice, red and white wine [12]. ...
... % for injectable solutions, 0.015-0.050 % for ophthalmological products and 0.015-0.20 % for syrups and suspensions [12]. ...
... They are found mainly in mascara, lipstick, foundation, facial cleansers, skin lighteners, underarm deodorant, eye makeup products, face lotion, condition shampoo, body lotion, toothpaste and hard soaps (Kirchhof and de Gannes 2013;Lin et al. 2011b;Arslan et al. 2019). Aside personal care products, parabens have also been found naturally in Bourbon vanilla, botrytized wine, white wine, yellow passion fruit juice and cloudberry (Soni et al. 2002). Parabens could also be found in the effluents of some other industries that utilize them as part of their additives or preservatives (Terasaki and Makino 2008;Canosa et al. 2006;Fernandes et al. 2020d). ...
... Although these products could be banned from the environment, the difficulties in effecting this ban are connected to their useful properties in numerous applications. Parabens are usually the first Fig. 1 General structure of the parabens found in the environment choice by many industries due to their unique properties which includes, tastelessness, lack of smell, low production cost, good water solubility, inertness and chemical stability over a wide temperature range (Soni et al. 2002;Li et al. 2020a;Terasaki et al. 2009a). Also, parabens do not alter the color of their products. ...
... The length of the alkyl chain also determines the ease of nucleation of parabens because as the alkyl chain length decreases, parabens' nucleation becomes more difficult (Yang et al. 2014b(Yang et al. , 2018a. The solubility of parabens in water is low compared to oil with increased chain length (Lin et al. 2011a;Soni et al. 2002). However, the efficiency of parabens as preservatives depends on their solubility in water phase (Soni et al. 2002). ...
Article
Personal care products such as soaps, tooth paste and shampoo often contain pollutants such as parabens, which refer to the esters of parahydroxylbenzoic acid, and end up contaminating waters. Parabens react with halogens to produce compounds that are often more toxic and persistent. Here we review properties, toxicity, analysis and remediation of parabens and halogenated parabens, with focus on photocatalysis using titanium oxide, graphene oxide and graphitic carbon nitride. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
... The Staphylococcus epidermis plays a major role in foot odor through the conversion of leucine, present in the sweat, into isovaleric acid, a volatile organic compound with a sour and pungent odor (Ara et al., 2006). Methylparaben is a common substance added to cosmetics with antimicrobial activity through the disruption of the plasmatic membrane and the denaturation of enzymes (Soni et al., 2002). Although there are no studies showing the acute toxicity or accumulation of this substance in animal models (Soni et al., 2002), research relating to the replacement or reduction of this chemical for plant-extracted compounds is on-going. ...
... Methylparaben is a common substance added to cosmetics with antimicrobial activity through the disruption of the plasmatic membrane and the denaturation of enzymes (Soni et al., 2002). Although there are no studies showing the acute toxicity or accumulation of this substance in animal models (Soni et al., 2002), research relating to the replacement or reduction of this chemical for plant-extracted compounds is on-going. An in vitro research conducted by Santoso and Riyanta (2019) in Indonesia revealed that a foot sanitizer spray using the ethanolic extract from coffee beans and ginger showed significant antimicrobial activity against S. epidermis. ...
Article
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This systematic scoping review presents evidence from 52 primary research articles for the beneficial, and sustainable, use of coffee in personal care products. The identification and evaluation of natural ingredients that harbor bioactive compounds capable of supporting healthy personal care and protecting and improving the appearance and condition of skin and hair is topical. Demand for natural and sustainable ingredients in beauty and personal care products is driving growth in a market valued at over $500 billion. Coffee, as one of the world's favorite beverages, is widely studied for its internal benefits. External benefits, however, are less known. Here the potential of coffee and its by-products as ingredients in cosmetic and personal care formulations is explored. Diverse applications of a range of bioactive compounds from the coffee bean, leaves, and by-products, are revealed. Research is evaluated in light of economic and environmental issues facing the coffee industry. Many of the 25 million smallholder coffee farmers live in poverty and new markets may assist their economic health. Coffee by-products are another industry-wide problem, accounting for 8 million tons of residual waste per year. Yet these by-products can be a rich source of compounds. Our discussion highlights phenolic compounds, triacylglycerols, and caffeine for cosmetic product use. The use of coffee in personal care products can benefit consumers and industry players by providing natural, non-toxic ingredients and economic alternatives and environmental solutions to support sustainability within the coffee production chain. Database searches identified 772 articles. Of those included (k = 52), a minority (k = 10; N = 309) related to clinical trials and participant studies. Applications were classified, using the PERSOnal Care products and ingredients classification (PERSOC). Sustainability potential was evaluated with the Coffea Products Sustainability (COPS) model. Overall objectives of the systematic scoping review were to: (1) scope the literature to highlight evidence for the use of coffee constituents in externally applied personal care products, and (2) critically evaluate findings in view of sustainability concerns.
... decyl-paraben) induce the release of histamine [16]. For instance, heptyl-paraben, another long alkyl chain paraben used as food additive, has been reported to induce a strong allergic reaction on animal skin [83]. Other research has shown genotoxic and cytotoxic effects of parabens on human lymphocytes in vitro and capacity to supress immune response [83]. ...
... For instance, heptyl-paraben, another long alkyl chain paraben used as food additive, has been reported to induce a strong allergic reaction on animal skin [83]. Other research has shown genotoxic and cytotoxic effects of parabens on human lymphocytes in vitro and capacity to supress immune response [83]. ...
Article
Endocrine-disrupting chemicals (EDCs), chemicals that can interfere with endogenous hormones and that are present in many consumer products, can affect the development and functions of the immune system. The prenatal period is critical because exposure to EDCs can induce irreversible changes in the immune system and increase the susceptibility of asthma and allergies later in life. Non-persistent EDCs are of most concern due to their high annual production and potential toxicity. In this review, we summarize the literature on the effects of prenatal exposure to non-persistent EDCs, namely phthalates and phenols, on asthma and allergic diseases, describe the biological mechanisms, and develop recommendations. Between 2011 and 2020, a total of 19 prospective studies were published. Most of them were focused on phthalates and bisphenol A and few on other bisphenols, parabens, triclosan, and benzophenone-3. Overall, the evidence is still insufficient due to differences in chemicals use between countries, sociodemographic characteristics of the populations, exposure misclassification due to the high within-subject variability, and heterogeneity on health outcome definitions. EDCs can alter airway cell differentiation, shift immune response towards Th2, alter T regulatory and Th17 expression, reduce innate immunity, and alter gut microbiota. Studies with a thoughtful exposure assessment design, a good characterization of the asthma and allergic phenotypes, and which consider biological mechanisms and EDCs mixtures are needed to better understand the burden of EDCs on the respiratory and immune systems. This research will contribute to implement public health policies to reduce EDCs exposure in the community, particularly in pregnant women.
... Chemically, parabens are the esters of p-hydroxibenzoic acid which contain different alkyl groups, for instance, methylparaben (MP), ethylparaben (EP), propylparaben (PP), butylparaben (BP), benzylparaben (BeP), heptylparaben (HP), isobutylparaben (IBP) and isopropylparaben (IPP) [11]. Among them, MP, EP, PP and BP are the most frequently and repeatedly used in combination with others in the final products [12]. However, the antimicrobial activity increases when using them in a mixture of two or more parabens [12]. ...
... Among them, MP, EP, PP and BP are the most frequently and repeatedly used in combination with others in the final products [12]. However, the antimicrobial activity increases when using them in a mixture of two or more parabens [12]. Owing to their extensive application, the potential damaging health effects ascribed to parabens could be augmented [13,14]. ...
Article
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Isothiazolinones methylisothiazolinone (MI) and methylchloroisothiazolinone (MCI), and parabens methylparaben (MP), ethylparaben (EP), propylparaben (PP) and butylparaben (BP) are the most common synthetic preservatives. They are all known to be potential skin allergens that lead to contact dermatitis. Thus, the identification of these unsafe chemicals in cosmetic products is of high importance. In the present study, solid-phase extraction (SPE) based on HyperSep reversed- phase C8/benzene sulfonic acid ion exchanger (HyperSep C8/BSAIE) and Sep-Pak C18 sorbents, and ultra-high performance liquid chromatography/diode array detector (UHPLC/DAD) were optimized for the simultaneous determination of MI, MCI, MP, EP, PP and BP in cosmetic products. HyperSep C8/BSAIE and UHPLC/DAD with the eluting solvent mixture (acetonitrile/methanol, 2:1, v/v) and detection wavelength (255 nm) were found to be the optimal conditions, respectively. The method illustrates the excellent linearity range (0.008–20 μg/mL) with coefficient of determination (R2, 0.997–0.999), limits of detection (LOD, 0.001–0.002 μg/mL), precision in terms of relative standard deviation (RSD < 3%, intra-day and <6%, inter-day) when examining a standard mixture at low (0.07 μ g/mL), medium (3 μ g/mL) and high (15 μ g/mL) concentrations. A total of 31 cosmetic samples were studied, achieving concentrations (MI, not detected (nd)-0.89 μg/g), (MCI, nd-0.62 μg/g), (MP, nd-6.53 μg/g), (EP, nd-0.90 μg/g), (PP, nd-9.69 μg/g) and (BP, nd-17.80 μg/g). Recovery values ranged from 92.33 to 101.43% depending on the types of sample. To our knowledge, this is the first specific method which covers the theme and describes background amounts of such preservatives in cosmetics.
... Further, parabens are chemically stable, non-volatile and odourless; they are generally of very low systemic toxicity upon short-or long-term exposure, and they lack allergic potential (Hafeez and Maibach 2013;Soni et al. 2005;Fransway et al. 2019a, b). Parabens with different n-alkyl chain lengths ranging from methyl paraben, ethyl paraben, propyl paraben to butyl paraben have been widely and safely used for many decades as preservatives in a variety of cosmetics, foods, beverages and pharmaceuticals (Soni et al. 2001(Soni et al. , 2002(Soni et al. , 2005. ...
... Assessments of shorter-chained linear n-alkyl parabens in OECD CF Level 3 rodent uterotrophic assays yielded equivocal results (Routledge et al. 1998;Soni et al. 2001Soni et al. , 2002CIR 2008CIR , 2019Ohta et al. 2012). ...
Article
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This article presents the outcomes of higher-tier repeated-dose toxicity studies and developmental and reproductive toxicity (DART) studies using Wistar rats requested for methyl paraben and propyl paraben under the European Union chemicals legislation. All studies revealed no-observed adverse effects (NOAELs) at 1000 mg/kg body weight/day. These findings (absence of effects) were then used to interpolate the hazard profile for ethyl paraben, further considering available data for butyl paraben. The underlying read-across hypothesis (all shorter-chained linear n -alkyl parabens are a ‘category’ based on very high structural similarity and are transformed to a common compound) was confirmed by similarity calculations and comparative in vivo toxicokinetics screening studies for methyl paraben, ethyl paraben, propyl paraben and butyl paraben. All four parabens were rapidly taken up systemically following oral gavage administration to rats, metabolised to p -hydroxybenzoic acid, and rapidly eliminated (parabens within one hour; p -hydroxybenzoic acid within 4–8 h). Accordingly, for ethyl paraben, the NOAELs for repeated-dose toxicity and DART were interpolated to be 1000 mg/kg body weight/day. Finally, all evidence was evaluated to address concerns expressed in the literature that parabens might be endocrine disruptors. This evaluation showed that the higher-tier studies do not provide any indication for any endocrine disrupting property. This is the first time that a comprehensive dataset from higher-tier in vivo studies following internationally agreed test protocols has become available for shorter-chained linear n -alkyl parabens. Consistently, the dataset shows that these parabens are devoid of repeated-dose toxicity and do not possess any DART or endocrine disrupting properties.
... Both MPB and TCS are members of the phenols/alcohols chemical class of preservatives and have distinct mechanisms of antimicrobial action. TCS blocks lipid biosynthesis in bacteria by specifically inhibiting the enzyme enoyl-acyl carrier protein reductase (6,7), whereas MPB exerts its inhibitory activity on membrane transport and mitochondrial function and is more active against fungi than bacteria (8). ...
... Few studies have addressed the mechanisms through which MPB and TCS exert their antifungal activities. MPB was shown to perturb microbial membrane function (8), and its effect on microbial membranes was recently tested in two-dimensional lipid systems, called the Langmuir monolayers (38), mimicking Staphylococcus aureus, Pseudomonas aeruginosa, and C. albicans membranes. Although MPB was shown to be more active against fungi than against bacteria, the strongest destructive effect of MPB was observed on bacterial membranes (38), suggesting that MPB may act differently on C. albicans. ...
Article
Preservatives increase the shelf life of cosmetic products by preventing growth of contaminating microbes, including bacteria and fungi. In recent years, the Scientific Committee on Consumer Safety (SCCS) has recommended the ban or restricted use of a number of preservatives due to safety concerns. Here, we characterize the antifungal activity of Ethylzingerone (Hydroxyethoxyphenyl butanone, HEPB), an SCCS-approved new preservative for use in rinse-off, oral care and leave-on cosmetic products. We show that HEPB significantly inhibits growth of Candida albicans , Candida glabrata and Saccharomyces cerevisiae , acting fungicidally against C. albicans . Using transcript profiling experiments, we found that the C. albicans transcriptome responded to HEPB exposure by increasing the expression of genes involved in amino acid biosynthesis, while activating pathways involved in chemical detoxification/oxidative stress response. Comparative analyses revealed that C. albicans phenotypic and transcriptomic responses to HEPB treatment were distinguishable from those of two widely used preservatives, triclosan and methylparaben. Chemogenomic analyses, using a barcoded S. cerevisiae non-essential mutant library, revealed that HEPB antifungal activity strongly interfered with the biosynthesis of aromatic amino acids. The trp1 Δ mutants in S. cerevisiae and C. albicans were particularly sensitive to HEPB treatment, a phenotype rescued by exogenous addition of tryptophan to the growth medium, providing a direct link between HEPB mode-of-action and tryptophan availability. Collectively, our study sheds light on the antifungal activity of HEPB, a new molecule with safe properties for use as a preservative in cosmetics industry, and exemplifies the powerful use of functional genomics to illuminate the mode-of-action of antimicrobial agents.
... However, common for all chemicals were higher concentrations observed for adults compared to adolescents. Further, we found a higher concentration of MPB than for PPB, but with a strong correlation between them, probably explained by the fact that MPB and PPB often are used in combination in the products [6,42]. A study from Denmark, assessing paraben content in cosmetic Table 6 Associations between urine biomarkers of chemical exposure and current asthma in adult participants products, showed that nearly all leave-on products contained parabens [43]. ...
... We found a strikingly high correlation between frequency of use of personal care products and urinary levels of parabens, especially for leave-on products. Both MPB and PPB are permitted for use as direct food additives and as indirect food additives in food packaging materials [6,42]. However, it has been indicated that only 0.6-0.8% of the total paraben exposure are dietary exposure and in a previous study no association between concentration of parabens in food and packing materials was found [45]. ...
Article
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Background Many phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index. Methods Demographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10–17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry. Results Detection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant. Conclusions Reported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.
... Paraben biotransformation studies reported that more than 90 % of parabens are excreted in the urine as conjugates (glucuronide and sulphate conjugates), whereas only a small fraction is left unconjugated (21). It is also considered that conjugated parabens have no biological activity (21,22). The penetration of parabens through the skin varies, and also shows the difference between species (16)(17)(18). ...
... From the available in vivo carcinogenicity studies on methyl-, ethyl-and propylparaben it can be concluded that they are not considered to be carcinogenic (8,10,16,17,22). ...
Article
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Effects of paraben toxicity, i.e., endocrine-disruption properties, are in the focus of researchers for decades, but still – they are a hot subject of debate. Parabens are aliphatic esters of p-hydroxybenzoic acid, which are widely used as antimicrobial agents for the preservation of cosmetics, pharmaceuticals and foods. Mostly used parabens are methyl-, ethyl-, propyl- and butylparaben. Although the toxicity of parabens is reported in animals and in in vitro studies, it cannot be taken for granted when discussing hazards for human health due to an unrealistic exposure-safety profile. Many studies have demonstrated that parabens are non-teratogenic, non-mutagenic, non-carcinogenic and the real evidence for their toxicity in humans has not been established. For now, methyl-, ethyl- and propylparaben are considered safe for use in cosmetics and pharmaceuticals within the recommended range of doses. Regarding alternatives for parabens, a variety of approaches have been proposed, but every substitute would need to be tested rigorously for toxicity and safety.
... It has been used as a food preservative due to its stability and non-volatility, and its antibacterial capabilities. [21,22] Due to its representation of the basal salivary flow rate, unstimulated saliva was employed in the parameter analysis. Saliva was collected using sterile syringes to prevent crosscontamination. ...
Article
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Context: In light of the widespread availability of anti-Streptococcus prophylactic drugs, researchers have begun to focus on developing newer, more effective agents that are also less expensive, more efficient, and safer. Aims: The purpose of this research was to assess the antibacterial activity of a multi-herbal mouth rinse to that of certain standard chemical formulations, including those based on essential oils, fluoride, and 0.2% chlorhexidine digluconate. It is a randomized, controlled, triple-blind experiment of several settings. Methodology: A total of 120 adolescents, aged 15 to 17, were randomly assigned to one of four treatment groups: The recommended dosing schedule is as follows: (a) 15 ml of a multiherbal mouth rinse twice daily; (b) 15 ml of a 0.2% chlorhexidine mouth rinse twice daily; (c) 15 ml of an essential oil mouth rinse twice daily; and (d) 15 ml of a 0.2% sodium fluoride mouth rinse twice daily. The number of oral streptococci CFUs/mL was determined from samples of subject saliva and plaque cultured on TYCSB agar. Statistical Analysis Used: The different mouthrinses were compared using repeated-measures analysis of variance (ANOVA), with the multi-herbal mouthrinse being compared using the Bonferroni post hoc test. P 0.05 was chosen as the significant threshold. Results: The multi-herbal mouth rinse considerably reduced S although there was no statistically significant difference between groups in the pre-treatment measurements. mutans colony count compared to the other mouthrinses (with the exception of the fluoride mouthrinse) up to 1 week postrinsing. Conclusion: The number of S. mutans colony forming units (CFU) was reduced by both chlorhexidine and multiherbal mouth rinses.
... Parabens can be absorbed through ingestion, inhalation, and the skin. Parabens may cumulate in the body as a result of day-to-day use of parabencontaining products [125][126][127][128][129]. ...
Article
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Gestational diabetes mellitus (GDM) remains a significant clinical and public health issue due to its increasing prevalence and the possibility for numerous short- and long-term complications. The growing incidence of GDM seems to coincide with the widespread use of endocrine disrupting chemicals (EDCs). The extensive production and common use of these substances in everyday life has resulted in constant exposure to harmful substances from the environment. That may result in epigenetic changes, which may manifest themselves also after many years and be passed on to future generations. It is important to consider the possible link between environmental exposure to endocrine disrupting chemicals (EDCs) during pregnancy, epigenetic mechanisms and an increased risk for developing gestational diabetes mellitus (GDM). This manuscript attempts to summarize data on epigenetic changes in pregnant women suffering from gestational diabetes in association with EDCs. There is a chance that epigenetic marks may serve as a tool for diagnostic, prognostic, and therapeutic measures.
... These two parabens are among the most commonly used in cosmetics and the most frequently, and in the highest concentration detected in the human body [20,21,24,25,27]. Since the most common preservative system in cosmetic formulations contains 0.3% MP and 0.1% PP [20,33] (Table S1), parabens in the same ratio (3:1) were also used in our study to more realistically reflect the exposure of human to parabens via cosmetics. However, the most important assumption of this study was that RA, which has multidirectional biological activity, can counteract the negative changes caused by parabens in the skin cells. ...
Article
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Parabens, which are widely used in food, medicines and cosmetics, have a harmful effect on human health. People are most exposed to parabens transdermally by using cosmetic products containing these preservatives. The purpose of this study was to estimate the influence of parabens (methylparaben—MP and propylparaben—PP) on the metabolism of collagen in the human skin fibroblasts and above all, to assess whether rosmarinic acid (RA—50, 100, or 150 M) can protect these cells from the adverse effects of parabens (0.001% MP and 0.0003% PP, 0.003% MP and 0.001% PP, and 0.01% MP and 0.003% PP). The possible mechanisms of RA action were estimated as well. Parabens decreased the expression of collagen type I and III at mRNA and protein levels, while RA (depending on the concentration) provided partial or total protection against these changes. The effective protection against the adverse effects of parabens on cell viability and proliferation was also provided by RA. The beneficial impact of RA on collagen and the fibroblasts resulted from an independent action of this compound and its interaction with parabens. This study allows us to conclude that this polyphenolic compound may protect from unfavorable health outcomes caused by lifetime human exposure to parabens contained in cosmetic products.
... They are safe to use (i.e. relatively non-irritating, non-sensitizing, and low-toxic) and there have been several safety assessments on these substances by a diversity of T agencies, including FAO/WHO, FDA and FEMA [8][9][10]. ...
Article
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Propylparaben, a commonly used antimicrobial preservative, has been reported as an anticonvulsant agent targeting neuronal Na⁺ channels (NaV). However, the specific features of the NaV channel inhibition by this agent have so far not been extensively studied. Moreover, it is still unclear if it shares this pharmacological activity with other parabens. Here, we fully characterized the mechanism of action of the inhibitory effect that propylparaben and benzylparaben induce on human NaV 1.2 channel isoform (hNaV1.2). We established a first approach to know the parabens structural determinants for this channel inhibition. The parabens effects on hNaV1.2 channel mediated currents were recorded using the patch-clamp whole-cell configuration on hNaV1.2 stably transfected HEK293 cells. Propylparaben induced a typical state-dependent inhibition on hNaV1.2 channel carried current, characterized by a left-shift in the steady-state inactivation curve, a prolongation in the time needed for recovery from fast inactivation and a frequency-dependent blocking behavior. The state-dependent inhibition is increased for butylparaben and benzylparaben and diminished for methylparaben, ethylparaben and p-hydroxybenzoic acid (the major metabolite of parabens hydrolysis). Particularly, butylparaben and benzylparaben shift the steady-state inactivation curve 2- and 3-times more than propylparaben, respectively. Parabens are blockers of hNaV1.2 channels, sharing the mechanism of action of most of sodium channel blocking antiseizure drugs. The potency of this inhibition increases with the size of the lipophilic alcoholic residue of the ester group. These results provide a basis for rational drug design directed to generate new potential anticonvulsant agents.
... To preserve the best condition; propylparaben was used as a preservative because exhibits a broad spectrum of antimicrobial activity and could prevent the contamination of bacteria that possibly occurs from the natural oil in the formula. Even some studies indicated that paraben is possibly toxic but in a population with normal skin, the paraben is practically non-irritating and non-sensitizing (Soni et al., 2002). While the Amesiodendron chinense (Merr.) ...
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Amesiodendron chinense (Merr.) Hu oil is reported to use for the treatment of skin disease by Thai folk medicine. Its hydrophilic-lipophilic balance (HLB) value is very important for developing a stable cream formulation. This study aimed to determine the required hydrophilic-lipophilic balance (rHLB) value of Amesiodendron chinense (Merr.) Hu oil and to develop a stable cream formulation. Herbal cream containing Amesiodendron chinense (Merr.) Hu oil was prepared by phase inversion temperature technique using water, Tween80, and Span60. The first series of 11 emulsions with HLB values ranging from 5.0 to 15.0 and the second series of eight emulsions with a smaller interval in HLB values from 5.0 to 7.8 were prepared. rHLB of coconut oil was also determined for validation of methodology. Creaming index is the established parameter to determine rHLB and to develop stable emulsion. Emulsions with optimum emulsifier concentration resulted in less percentage-creaming index. Utilizing determined rHLB, Amesiodendron chinense (Merr.) Hu cream was formulated and evaluated for different physical parameters including viscosity, color, odor, texture, and pH. Finally, the results showed the rHLB value of coconut oil and Amesiodendron chinense (Merr.) Hu oil was 5.4 and 6.2, respectively. The stable creams were developed with a 3% emulsifier. Physical parameters were found to be consistent over 6 cycles of accelerated stability test under 4 and 45 ○ C. Physical properties of cream evaluation ensure the stability of the developed cream. rHLB value of Amesiodendron chinense (Merr.) Hu oil was exhibited, and the stable creams were successfully formulated by utilizing determined rHLB.
... However, due to the wide use of parabens, humans are at high risk of exposure to these compounds which can be entered to the body through different ways of dermal absorption, oral intake and inhalation (Soni et al. 2005;El Hussein et al. 2007). In this regard, previous studies conducted in the United States have shown an average exposure of 76 mg/day/person to the total parabens, of which cosmetics and personal care products (PCPs) contributes for 50 mg, and pharmaceuticals and foodstuffs account for 25 and 1 mg, respectively (Soni et al. 2002). ...
Article
Parabens are used as antimicrobial preservatives in a wide range of cosmetics, foodstuffs and pharmaceuticals. There is increasing evidence that has linked paraben exposure to adverse health effects. Therefore, this study aimed to evaluate the determinants of urinary parabens concentration among Iranian pregnant women. The urinary concentrations of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were measured among 117 pregnant women at their first trimester. The associations between urinary concentrations of these compounds with different variables were assessed. MeP, EtP, PrP, and BuP were detected with a median concentration of 160.1, 0.04, 7.8, and 7.5 μg/g.cre, respectively. Significant associations were observed between urinary concentrations of MeP and PrP with educational level, between MeP, PrP and BuP with plastic packaging of foodstuffs and physical activity status, and between MeP and sampling season. All the measured parabens were significantly correlated with the use of personal care products. PrP and BuP were found to be correlated to passive smoking and intake of supplements, respectively. MeP and EtP showed negative significant relationships with the consumption of drinking water and MeP concentration correlated with gestational age. According to our findings, Iranian pregnant women are at high risk of exposure to parabens.
... Esters are commonly used in different fields. [22][23][24][25] Among various types of esters, methyl esters exhibit unique biological activities and have been widely employed in the synthesis of pharmaceuticals 26,27 and polymers. 28,29 In the context of developing future biorefineries, selective esterification of C(OH)-C bonds is a very attractive option in terms of producing value-added chemicals from renewable resources, but it has not been reported so far. ...
Article
C(OH)–C bonds are widely distributed in naturally renewable biomass, such as carbohydrates, lignin, and their platform molecules. Selective cleavage and functionalization of C(OH)–C bonds is an attractive strategy in terms of producing value-added chemicals from biomass. However, effective transformation of alcohols into esters by activation of C(OH)–C bonds has not been achieved so far. Herein, for the first time, we report selective cleavage and esterification of C(OH)–C bonds, catalyzed by inexpensive copper salts, using environmentally benign oxygen as the oxidant, to afford methyl esters in excellent yields. A diverse range of phenylethanol derivatives that contain C(OH)–C bonds were effectively converted into methyl benzoates. Detailed analysis revealed that the high efficiency and selectivity resulted mainly from the fact that, in addition to the major esterification reaction, the side products (e.g., olefins and acids) were also transformed in situ into esters in the reaction system.
... MeP, EtP, and PrP were the major paraben analogs in the samples, accounted for 59%, 24%, and 10% of total paraben contents, respectively (Liao et al. 2013). The cytotoxic mechanism of parabens may be related to mitochondrial failure, which depends on the induction of membrane permeability transitions, accompanied by mitochondrial depolarization and the decoupling of cellular adenosine triphosphate (ATP) through oxidative phosphorylation (Soni et al. 2002). Some epidemiological surveys point that paraben exposures are associated with T2DM. ...
Article
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Type 2 diabetes mellitus (T2DM), one of the most common chronic metabolic diseases, involves a complex interaction among genetic, epigenetic, and environmental risk factors. The incidence and prevalence of T2DM are rapidly increasing globally. In recent years, increasing body of evidences from both human and animal studies have displayed an association between exposure to early unfavorable life factors such as endocrine-disrupting chemicals (EDCs) and the prevalence of T2DM in later life. The exogenous EDCs can lead to disadvantageous metabolic consequences because they interfere with the synthesis, secretion, transport, binding, action, and metabolism of endogenous hormones. EDCs also have long-term adverse effects on newborns, children, and adolescents by causing increased susceptibility to T2DM in adults. This review summarizes the most recent advances in this field, including diabetes-related EDCs (bisphenol A, phthalates, chlordane compounds, parabens, pesticides, and other diabetes-related EDCs), EDC exposure and gestational diabetes mellitus, prenatal and perinatal EDC exposures and T2DM, adult EDC exposure and T2DM, transgenerational effects of EDCs on T2DM as well as the possible diabetogenic mechanisms.
... 21 Nowadays, eco-friendly methods were investigated in order to find out alternative ways for paraben synthesis that need less energy and power consumption. 25 ...
Article
Cosmetics, cosmeceuticals, and variable healthcare products used parabens, among other excipients, for their preservative and antimicrobial activities. Paraben derivatives exhibit distinguished physiochemical properties that enable them to be compatible with the formulation of cosmetic agents in different dosage forms. In addition to their potency and efficacy, parabens are economically efficient as they have low manufacturing costs. Despite the desirable characteristics, the safety of parabens use is controversial after detecting these chemicals in various biological tissues after repetitive and long-term use of formulations containing them. The use of parabens drew public health attention after scientific reports linked skin exposure to parabens with health issues, in particular, breast cancer. In response, worldwide authorities set regulations for the allowance concentrations of paraben to be used in variable cosmetic products.
... Moreover, the GM has previously been considered as a reservoir for antibiotic resistance genes (Gibson et al., 2015;Anthony et al., 2021). Non-antibiotic antimicrobials, including MDCs triclosan and parabens, commonly used as preservatives in foods, food contact materials (FCMs) and personal care products (Soni et al., 2001(Soni et al., , 2002(Soni et al., , 2005Cosmetic Ingredient Review Expert Panel, 2008;Halden et al., 2017), may also contribute to AMR (Scientific Committee on Consumer Safety [SCCS], 2010). This is because some resistance mechanisms are common to both biocidal MDCs and antibiotics, for example, the former may; exert selective stress leading to the expression of bacterial resistance mechanisms and their dissemination, and/or; maintain mobile genetic elements carrying genes involved in antibiotic cross-resistance (Scientific Committee on Emerging and Newly Identified Health Risks, 2009). ...
Article
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Three areas of relevance to the gut microbiome in the context of One Health were explored; the incorporation of the microbiome in food safety risk assessment of xenobiotics; the identification and application of beneficial microbial components to various areas under One Health, and; specifically, in the context of antimicrobial resistance. Although challenging, focusing on the microbiota resilience, function and active components is critical for advancing the incorporation of microbiome data in the risk assessment of xenobiotics. Moreover, the human microbiota may be a promising source of beneficial components, with the potential to metabolize xenobiotics. These may have possible applications in several areas, e.g., in animals or plants for detoxification or in the environment for biodegradation. This approach would be of particular interest for antimicrobials, with the potential to ameliorate antimicrobial resistance development. Finally, the concept of resistance to xenobiotics in the context of the gut microbiome may deserve further investigation.
... found that the typical antibacterial chemicals that are used as preservatives in a range of cosmetics and personal care products, the parabens, were associated with the differential abundance of several bacteria genera. The main contributing source for human exposure to parabens and other antimicrobial chemicals are personal care products (Bledzka et al., 2014), but both MPB and PPB are permitted for use as direct food additives and as indirect food additives in food-packaging materials (Soni et al., 2001(Soni et al., , 2002. Urine biomarker levels of exposure to parabens correlate well with the reported frequency of use of personal care products (Vindenes et al., 2021). ...
Article
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Antimicrobial chemicals are used as preservatives in cosmetics, pharmaceuticals, and food to prevent the growth of bacteria and fungi in the products. Unintentional exposure in humans to such chemicals is well documented, but whether they also interfere with human oral microbiome composition is largely unexplored. In this study, we explored whether the oral bacterial composition is affected by exposure to antibacterial and environmental chemicals. Gingival fluid, urine, and interview data were collected from 477 adults (18–47 years) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan, triclocarban, parabens, benzophenone-3, bisphenols, and 2,4- and 2,5-dichlorophenols (DCPs) were quantified (by mass spectrometry). Microbiome analysis was based on 16S amplicon sequencing. Diversity and differential abundance analyses were performed to identify how microbial communities may change when comparing groups of different chemical exposure. We identified that high urine levels (>75th percentile) of propyl parabens were associated with a lower abundance of bacteria genera TM7 [G-3], Helicobacter, Megasphaera, Mitsuokella, Tannerella, Propionibacteriaceae [G-2], and Dermabacter, as compared with low propylparaben levels (<25th percentile). High exposure to ethylparaben was associated with a higher abundance of Paracoccus. High urine levels of bisphenol A were associated with a lower abundance of Streptococcus and exposure to another environmental chemical, 2,4-DCP, was associated with a lower abundance of Treponema, Fretibacterium, and Bacteroidales [G-2]. High exposure to antibacterial and environmental chemicals was associated with an altered composition of gingiva bacteria; mostly commensal bacteria in the oral cavity. Our results highlight a need for a better understanding of how antimicrobial chemical exposure influences the human microbiome.
... It has been used as a food preservative due to its stability and non-volatility, and its antibacterial capabilities. [21,22] Due to its representation of the basal salivary flow rate, unstimulated saliva was employed in the parameter analysis. Saliva was collected using sterile syringes to prevent crosscontamination. ...
Article
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Context: In light of the widespread availability of anti-Streptococcus prophylactic drugs, researchers have begun to focus on developing newer, more effective agents that are also less expensive, more efficient, and safer. Aims: The purpose of this research was to assess the antibacterial activity of a multi-herbal mouth rinse to that of certain standard chemical formulations, including those based on essential oils, fluoride, and 0.2% chlorhexidine digluconate. It is a randomized, controlled, triple-blind experiment of several settings. Methodology: A total of 120 adolescents, aged 15 to 17, were randomly assigned to one of four treatment groups: The recommended dosing schedule is as follows: (a) 15 ml of a multiherbal mouth rinse twice daily; (b) 15 ml of a 0.2% chlorhexidine mouth rinse twice daily; (c) 15 ml of an essential oil mouth rinse twice daily; and (d) 15 ml of a 0.2% sodium fluoride mouth rinse twice daily. The number of oral streptococci CFUs/mL was determined from samples of subject saliva and plaque cultured on TYCSB agar. Statistical Analysis Used: The different mouthrinses were compared using repeated-measures analysis of variance (ANOVA), with the multi-herbal mouthrinse being compared using the Bonferroni post hoc test. P 0.05 was chosen as the significant threshold. Results: The multi-herbal mouth rinse considerably reduced S although there was no statistically significant difference between groups in the pre-treatment measurements. mutans colony count compared to the other mouthrinses (with the exception of the fluoride mouthrinse) up to 1 week postrinsing. Conclusion: The number of S. mutans colony forming units (CFU) was reduced by both chlorhexidine and multiherbal mouth rinses.
... 12 Meanwhile, Methylparaben, which is an anti-fungal, was absorbed through the skin, hydrolyzed to p-hydroxybenzoic acid, and excreted without accumulating in the body. [28][29] DMSO was also widely used as a permeation enhancer of hydrophilic and hydrophobic drugs in the topical dosage form. Thus, in this study, it was used to increase the solubility and permeability of the hydrophobic and hydrophilic compounds contained in the extract. ...
... For both methyl and propyl paraben, males were higher in infancy, whereas females were far higher in adolescence and adulthood. Methyl paraben is one of the most frequently used preservatives in cosmetic products such as lipsticks, perfumes, and personal care products [80], thus potentially explaining the higher levels found in girls [81]. Ethyl paraben showed the highest concentrations in adults, where urinary levels were positively associated with the consumption of fast and canned foods. ...
Article
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The Korean National Environmental Health Survey (KoNEHS) program provides useful information on chemical exposure, serves as the basis for environmental health policies, and suggests appropriate measures to protect public health. Initiated on a three-year cycle in 2009, it reports the concentrations of major environmental chemicals among the representative Korean population. KoNEHS Cycle 3 introduced children and adolescents into the analysis, where the blood and urine samples of 6167 participants were measured for major metals, phthalates, phenolics, and other organic compounds. Lead, mercury, cadmium, metabolites of DEHP and DnBP, and 3-phenoxybenzoic acid levels of the Korean adult population tended to decrease compared to previous survey cycles but remained higher than those observed in the US or Canada. Both bisphenol A (BPA) and trans,trans-muconic acid concentrations have increased over time. Heavy metal concentrations (blood lead, and cadmium) in children and adolescents were approximately half that of adults, while some organic substances (e.g., phthalates and BPA) were high. BPA showed higher levels than in the US or Canada, whereas BPF and BPS showed lower detection rates in this cycle; however, as these are increasingly used as a substitute for BPA, further research is necessary. As environmental chemicals may affect childhood health and development, additional analyses should assess exposure sources and routes through continuous observations.
... Parabens boost shelf life and safety of personal care products and cosmetics, as they are highly effective in preventing the growth of bacteria, fungi and yeast that could cause spoilage of products. Generally, paraben concentration in formulations is up to 1%. Soni et al. (2002) had speculated that if the maximum amount of daily cosmetic and personal care product usage is approximately 50 g, and 10% of these contain parabens at the highest level (1%), then the possible exposure is 0.05 g (50 mg) per day. Paraben containing products may contact hair, scalp, lips, skin, mucosae (oral, ocular and vaginal), axillae and nails. ...
Article
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Parabens are commonly used as preservatives and antimicrobial compounds in cosmetic, pharmaceutical and food industries. Structurally they are similar to estrogen hormone and they interfere with nuclear receptors for androgens, estrogens, progesterone, glucocorticosteroids etc. Hence, they are considered as endocrine disrupting chemical (EDC)s. Studies in both human and rodents have established the role of parabens in altering steroidogenesis and activity of enzymes that metabolize endogenous hormones. Parabens disrupt normal function of the hormones and lead to reproductive, developmental and neurological disorders; thyroid related problems, skin allergy and cancers. Scientific articles supporting these assertions have led some countries banning or restricting paraben usage. A number of substitutes, both natural and synthetic chemicals are now in market as alternatives of parabens. This review article aims to provide adverse effects of paraben as well as potent paraben alternatives. The major alternatives include formaldehyde, triclosan and phenol, but those chemicals also have toxicity and side effects which are difficult to ignore. Moreover, the natural compounds have low shelf life and less potency. Therefore, more research is needed to establish the alternatives of parabens.
... Other studies pointed out that PBs may interfere with the microorganisms respiration (25,26,30,31) by the inhibition of mitochondria oxygen consumption in fungi, especially in mitochondrial complex II (24,27); however, it Annexes 207 was also postulated that the mode of action of aliphatic PBs was based on their ability to disrupt a cell membrane by the modification of its integrity and permeability (32,33), the induction of a potassium efflux (34), or the alteration of the transmembranal potential (23,25,26). These substances may have multiple biological effects, but their inhibitory effects on membrane transport and mitochondrial processes are considered essential for their antifungal activity (1, 24,30,35). ...
Thesis
Les microbiotes intestinal et cutané humains sont deux écosystèmes stables et propres à chaque individu. Néanmoins, il existe dans chacun d’eux, un socle de souches communes, le core microbiote. De nombreux facteurs exogènes, comme les xénobiotiques, peuvent perturber et influencer la composition des microbiotes et provoquer une dysbiose, pouvant participer à plusieurs pathologies. En outre, ces microorganismes peuvent métaboliser, voire dégrader ces composés les rendant ainsi inactifs. Il est donc important de pouvoir mettre en évidence les effets potentiels des xénobiotiques sur les bactéries mais également d’identifier les souches responsables de la métabolisation des composés. Les buts de la thèse ont été la mise en place de modèle de microbiote intestinal et cutané, tout d’abord en individualisant les souches, puis en les regroupant en consortium afin de déterminer i- les effets de différents xénobiotiques sur les microbiotes et ii- l’impact de ces microbiotes sur les molécules testées. Un modèle représentatif du core microbiote intestinal composé de 30 souches ainsi qu’un modèle d’étude des souches individuelles a été en réalisé en microplaque dans un milieu unique. Les résultats ont montré que la croissance des 36 souches en culture unique ainsi que le consortium stabilisé de 30 souches est inhibée majoritairement en présence d’antibiotiques. L’analyse des surnageants de culture (souches uniques ou consortium) par UHPLC-MS/MS a, quant à elle, révélé que des xénobiotiques peuvent être modifiés chimiquement par les bactéries. Concernant le modèle cutané, nous avons mis en évidence que les parabènes n’ont pas d’action sur les staphylocoques du microbiote cutané mais que des modifications de structure de ces perturbateurs endocriniens sont retrouvés en présence de nombreuses souches bactériennes.Sur la base de nos résultats, ce modèle simplifié pourrait permettre à terme de faciliter l’étude de l’impact des xénobiotiques sur certains microbiotes, facilitant certaines étapes du développement de nouvelles thérapies.
Article
Aim To evaluate the tissue response promoted by Bio‐C Pulpo (Bio), MTA Repair HP (MTA‐HP) and White MTA (WMTA) and whether these materials cause liver changes in a rat experimental model. Methodology Polyethylene tubes filled with Bio, MTA‐HP and WMTA, and empty tubes (control group, CG) were implanted into the subcutaneous of tissues of rats for 7, 15, 30 and 60 days. Inflammatory reaction score (IRS), capsule thickness, number of inflammatory cells (IC), von Kossa reaction, interleukin‐6 (IL‐6) and alkaline phosphatase (ALP) immunohistochemistry reactions were performed. Combined methods, von Kossa followed by immunohistochemistry for detection of ALP, were performed. At 60 days, the serum glutamic‐oxaloacetic transaminase (GOT) and glutamic‐pyruvic transaminase (GPT) levels were measured and liver fragments were collected for histological analysis; the data were assessed by One‐Way ANOVA analysis followed by Sidak’s post‐test. The biocompatibility and bioactivity data were subjected to the two‐way ANOVA analysis followed by Tukey post‐hoc test, except the IRS. The IRS data were subjected to the Kruskal‐Wallis ANOVA non parametric test followed by Dunn’s test (p ≤ 0.05). Results No significant difference was detected in serum GOT and GPT concentrations and in the number of hepatocytes among the experimental and CG samples. Although Bio‐C Pulpo had the highest IC and IL‐6‐immunolabelled cells (p < 0.0001) at all periods, no significant difference was observed in the IRS among the materials, except at 60 days. In this period, the WMTA had lower IRS. All groups had a significant reduction in the capsule thickness and in the number of IC and IL‐6‐immunolabelled cells over time. Bio‐C Pulpo, MTA‐HP and WMTA specimens had greater immunoexpression of ALP than CG (p˂0.0001). At all periods, von Kossa‐positive and birefringent structures were observed in the capsules around the materials. ALP‐immunolabelled cells were also seen near to von Kossa‐positive structures. Conclusions Bio‐C Pulpo, MTA‐HP and WMTA materials did not cause morphological changes in the liver as well as no significant alteration in the serum GOT and GPT levels. Moreover, these bioceramic materials were biocompatible and exhibited bioactive potential. However, Bio‐C Pulpo induced greater inflammatory infiltrate than MTA‐HP and WMTA at all periods.
Article
Methyl- and propyl- parabens are generally regarded as safe by the U.S Food and Drug Administration and as such are commonly used in personal care products. These parabens have been associated with increased white adipogenesis in vitro and methyl paraben also increased the white adipose mass of mice. Given brown adipose also plays a role in energy balance, we sought to evaluate whether the effects of methyl- and propyl- parabens on white adipocytes extended to brown adipocytes. We challenged white and brown pre-adipocytes at low doses of both parabens (up to 1 < mu > M) during the differentiation process and examined adipogenesis with the ORO assay. The impact of each paraben on glucose uptake and lipolytic activity of adipocytes were measured with a fluorescent glucose analog and enzymatically, respectively. Methyl- and propyl- parabens increased adipogenesis of 3T3-L1 white adipocytes but not brown adipocytes. In white adipocytes, methyl paraben increased glucose uptake and both parabens reduced basal lipolysis. However, in brown adipocytes, parabens had no effect on basal lipolysis and instead attenuated isoproterenol induced lipolysis. These data indicate that methyl- and propyl- parabens target the differentiation and metabolic processes of multiple types of adipocytes in a cell autonomous manner.
Article
A fast methodology for the assay of parabens in drug and cosmetic preparations has been presented. The procedure developed is based on paper spray tandem mass spectrometry and isotope dilution approach. For each investigated paraben, the corresponding labeled standard has been used in order to improve the accuracy and reproducibility of the analyses. The MS experiments have been performed under MRM conditions, monitoring the transitions [M‐H]‐ → m/z 92 and [M‐H]‐ → m/z 98, respectively for each analyte and the corresponding labeled internal standard. The quantitative assay has been performed using a calibration curve built from 2 mg/L to 15mg/L. The method accuracy, in all case near 100%, was evaluated using fortified samples at two concentration levels, which are representative of the lower and the higher portion of calibration curve. The good values of LOQ, LOD and reproducibility confirm the consistency of the developed approach.
Article
Anthropogenic chemicals such as parabens and triclosan are used in personal care products. Due to their ability to decrease or prevent bacterial contamination and act as preservatives, these chemicals are used in cosmetic manufacturing processes to increase the shelf life of products. In this study, we assessed the side effects of environmental estrogens (such as the xenoestrogen butylparaben and the antimicrobial agent and preservative triclosan) on thyroid function, brain monoamine levels, and DNA aberration. Forty‐two male albino rats were divided into seven groups with six members each: the first group served as control; the second and the third groups were treated with butylparaben 10 and 50 mg/kg body weight, respectively; the fourth and fifth groups were treated with triclosan 10 and 50 mg/kg body weight, respectively; and the sixth and seventh groups were treated with butylparaben plus triclosan 10 and 50 mg/kg body weight, respectively. After 60 days, blood samples were collected and brain specimens were divided into striatum, midbrain, cortex, and thalamus. Thyroid function and levels of monoamines and monoamine metabolites were determined for each brain area. Comet assay was used for brain tissue analysis. The results showed that butylparaben and triclosan and their combinations induced hypothyroidism and disrupted monoamine levels, leading to a decrease in catecholamine and serotonin levels, and accelerated production of 5‐hydroxyindoleacetic acid. The obtained data indicate that anthropogenic chemicals such as butylparaben and triclosan have harmful effects on thyroid and brain function and accelerate cell destruction and mutation, as evidenced by single‐stranded DNA breaks in the comet assay.
Article
Limited information is available about the levels of exposure of paraben and bisphenols emerging from PCPs use in Indian women and the risk associated with it. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the concentrations of six parabens (methyl-, ethyl-, propyl-, butyl, benzyl-, and heptyl-parabens) and 8 bisphenols (Bisphenol A, B, F, P, S, Z, AP, and AF) in PCPs samples (n = 114) obtained from Indian market and in the urine samples of young adult females (n = 52). The concentrations measured in PCPs and urine samples were used to determine the estimated daily intake. The mean concentrations of 6 parabens and 8 bisphenols in PCPs ranged from 38.3 to 2.38 × 10⁵ ng/mL and 2.71–148 ng/mL, respectively. In urine samples analysed, the mean concentrations of 6 parabens and 8 bisphenols ranged from 0.007 to 293 ng/mL and 0.10–10.77 ng/mL, respectively. There was no significant correlation of EDCs with age, BMI and waist-to-hip ratio (WHR), but significant correlations (p < 0.05) were observed between urinary paraben and bisphenol concentrations. A statistically significant difference (p < 0.05) exists between the BMI and WHR groups by bisphenol concentrations. Estimated daily intake and exposure risks for parabens and bisphenols revealed no possible concerns for Indian young adult females. Hitherto, this is the first study to show that Indian young adult females were exposed to parabens and bisphenols. This study provides evidence on PCPs usage contribute to the urinary concentrations of EDCs.
Article
The commercial use of entomopathogenic nematodes after mass production requires the development of formulation techniques that extend nematode survival and prevent virulence loss during storage. In this study, the room temperature viability of Steinernema yirgalemense, in diatomaceous earth (DE), was investigated. The shelf life was maintained above 70% mean survival rate by week 4. To avoid microbial contamination, the direct effect of antifungal agents, peroxyacetic acid (PAA), trans-cinnamic acid (TCA) and nipagin on the efficacy of the infective juveniles (IJs) was preliminarily investigated. Short-term exposure of PAA lowered the efficacy of IJs, yet low concentrations of TCA and nipagin had no effect. Finally, the combined effect of DE and nipagin on IJ efficacy was assessed. High concentrations of nipagin in DE killed all the IJs in the first week of storage. Lower concentrations of nipagin in DE have potential to be incorporated in EPN products.
Article
Acne and dandruff are common skin problems often treated by using various cosmetic products containing antimicrobial agents. The demand for more and more cosmetics from plant sources is continuously increasing, hence the present study was undertaken to investigate antimicrobial activity of Ajowan oil against cosmetically important microorganisms by agar diffusion method and measurement of zone of inhibition. Ajowan i.e dried ripe fruits of plant Trychyspermum ammi Sprague belonging to family Umbellifereae (also called Carum copticum, family Apiaceae) were collected from local market of Nagpur, Maharashtra, India and subjected to steam distillation, by using Clevenger apparatus to obtain Ajowan oil. The antimicrobial activity of Ajowan oil (100% concentration), different concentrations of Ajowan oil (1%, 0.75%, 0.5%, and 0.25% v/v) was determined by the agar well diffusion technique against microorganisms associated with acne and dandruff i.e. Propionibacterium acnes (MTCC 1951), Staphylococcus aureus (MTCC737), Staphylococcus epidermidis (MTCC 6810), Candida albicans (MTCC 227), Malassezia furfur (MTCC 1374), Malassezia furfur (MTCC 1765), and microorganisms mentioned in Bureau of Indian Standard guidelines for microbial testing and preservatives efficacy test of cosmetic formulations i.e. Pseudomonas aeruginosa (MTCC 1688), Escherichia coli (MTCC 1687), and Aspergillus niger (MTCC 10180). From present study of Ajowan oil against cosmetically important microorganisms, it was found that Ajowan oil (100% concentration) exhibited inhibitory activity against P. aeruginosa, S. aureus, S. epidermidis, E. coli, C. albicans, P. acnes, M. furfur 1374 and M. furfur 1765 except against A. niger. All the other concentrations of Ajowan oil i.e. 1%, 0.75%, 0.5%, 0.25%, exhibited inhibitory activity against P. aeruginosa, S. aureus, S. epidermidis, E. coli, C. albicans, and P. acne except against A. niger, M. furfur 1374 and M. furfur 1765. Hence Ajowan oil can be used as Antiacne agent in cosmetic formulations.
Chapter
Water is a basic necessity for living beings and vital for the existence of life on Earth. However, the growing development and consumption of chemicals in industries, agriculture, and domestic households is responsible for the increasing water contamination which is leaving a negative impact in the ecosystem. Use of contaminated water is giving birth to various waterborne diseases and deteriorating the natural environment for aquatic and marine life. Providing clean and freshwater for all has now become a challenging task. Several organic (organic dyes, pesticides, pharmaceutical ingredients, etc.) and inorganic (heavy metal ions, radioactive substances, etc.) contaminants are introduced into the freshwater resources from wastewater effluents. Treatment of effluents before discharging into freshwater bodies is one of the best approaches to reduce water pollution. To clean the wastewater, using several technologies, the basic understanding of functional groups and the nature of water contaminants is most important. Therefore this chapter provides a broad overview of classification, sources, structure, functional groups, and adverse effects on living beings of various water contaminants.
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Este artigo aborda a utilização de cosméticos faciais que contêm na formulação conservantes da classe dos parabenos. O proposito deste estudo é identificar os efeitos colaterais que estes conservantes podem ocasionar à saúde, ao serem aplicados sobre a pele. Este designo tem como base uma revisão bibliográfica, realizada através de livros e artigos científicos online. Nesta análise é possível compreender os conservantes mais comuns presentes nas formulações, bem como, o limite de porcentagem, sua toxicidade e os efeitos colaterais acumulativos no organismo humano.
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Aim To evaluate the cytotoxicity, biocompatibility and mineralization capacity of BIO-C PULPO, and MTA. Methodology L929 fibroblasts were cultured and MTT assay was used to determine the material cytotoxicity on 6, 24, and 48 h. A total of 30 male rats (Wistar) aged between 4 and 6 months, weighing between 250 and 300 g were used. Polyethylene tubes containing BIO-C PULPO, MTA, and empty tubes were implanted into dorsal connective tissue. After the experimental periods (7, 15, 30, 60, and 90 days) the tubes were histologically analyzed using hematoxylin-eosin (H&E), immunolabeling of IL-1β and TNF-α, and von Kossa staining, or without staining for polarized light analysis. The average number of inflammatory cells was quantified; the mineralization assessment was determined by the area marked in μm2 and semiquantitative immunolabeling analyses of IL-1β and TNF-α were performed. Then, data underwent statistical analysis with a 5% significance level. Results It was observed that BIO-C PULPO and MTA presented cytocompatibility at 6, 24, and 48 similar or higher than control for all evaluated period. On periods 7 and 15 days, BIO-C PULPO was the material with the highest number of inflammatory cells (p<0.05). On periods 30, 60, and 90 days, BIO-C PULPO and MTA presented similar inflammatory reactions (p>0.05). No statistical differences were found between Control, BIO-C PULPO, and MTA for immunolabeling of IL-1β and TNF-α in the different periods of analysis (p<0.05). Positive von Kossa staining and birefringent structures under polarized light were observed in all analyzed periods in contact with both materials, but larger mineralization area was found with BIO-C PULPO on day 90 (p<0.05). Conclusion BIO-C PULPO was biocompatible and induced mineralization similar to MTA.
Article
A green deep eutectic solvent-based vortex-assisted liquid-liquid microextraction (DES-VALLME) procedure for the determination of parabens in mouthwashes was developed. Deep eutectic solvents formed by combining DL-menthol and decanoic acid in different molar ratios were prepared, the highest extraction recovery was obtained with DES consisting of 4:1 molar ratio, and this DES was used as an extraction solvent for paraben determination in mouthwashes. The effect of parameters such as solution pH, mol ratio of DES composition, DES volume, vortex and centrifugation time and sample volume were examined. Optimum working conditions of the study; 400 µl DES, 3 min. vortex time, 5 min. centrifugation time, 5 ml sample volume were determined. The detection limit was in the range of 4.6-6.1 µg L⁻¹, while the RSDs values were in the range of 0.70-1.41% in intraday and 1.27-2.41% in interday. The method in the study was successfully applied for the determination of methyl, ethyl, propyl and butyl paraben in 10 different mouthwashes obtained from cosmetic stores.
Article
A new cocrystal comprising two pharmaceutically important molecules methyl‐4‐hydroxybenzoate (p‐MHB) (C8H8O3) and carbonyl diamide (urea) [CO(NH2)2] is crystallized together for the first time through restricted solvent evaporation method at ambient conditions. The single crystal X‐ray diffraction analysis shows that the engineered cocrystal p‐MHB:urea (1:1) (C9H12N2O4) crystallizes in monoclinic system with centrosymmetric space group C12/c1. The internal structure analysis shows that the urea molecule with its unique ability forms hydrogen bonding network throughout the cocrystal system. Different orientations of the identified synthons form the networks via supramolecular connections such as C═O⋯H─O and C═O⋯N─H. Correlation between the internal molecular configurations in the unit cell, protruding molecular groups on different growth faces, and attachment energies of different crystal planes is studied. The Hirshfeld surface analysis shows that the higher percentage of overall interactions between the carbon and oxygen atoms at the outer surfaces of the cocrystal induces further incorporation of molecular aggregation and crystal growth. The 2D finger print plots infer that about 90.9% of the overall interactions are mainly due to the H bonds. Differential scanning calorimetry analysis reveals that the grown cocrystal undergoes an observable phase transition at 105.65 °C prior to its melting endotherm that peaks at 110.29 °C. A new cocrystal comprising two pharmaceutically important molecules methyl‐4‐hydroxybenzoate(C8H8O3) and carbonyl diamine [CO(NH2)2] is crystallized for the first time. Its complete internal and external structure is analyzed through single crystal X‐ray diffraction and computational studies. The differential scanning calorimetry analysis reveals the thermal stability and a phase transition before the melting.
Article
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Objectives The aim of this study is to establish a sterilization method for cellulose nanofibers (CNFs) dispersions that uses multiple preservatives with different hydrophilicities without affecting the physical and chemical properties of CNFs, and to provide useful information for sample preparation in future toxicity study of CNFs. Methods Various preservatives were added to the phosphorylated CNF dispersions, endotoxin level and the numbers of bacteria and fungi in the CNF dispersion were analyzed. The pH values and viscosity of sterilized CNF dispersions were compared with those of control and autoclaved CNF dispersions. Results Phosphorylated CNF dispersions at a concentration of 2.0 mg/mL or lower and the addition of 10 µg/mL benzalkonium chloride alone or 250 µg/mL methyl parahydroxybenzoate and 250 µg/mL propyl parahydroxybenzoate in combination can sterilize CNF dispersions without changing the physical and chemical properties of CNFs. Conclusions We developed sterilization method for CNF dispersions that uses multiple preservatives with different hydrophilicities without affecting the physical and chemical properties of CNFs. This sterilization method for CNFs dispersions can be applied to the safety assessment of CNF with different physicochemical properties in the future.
Thesis
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Abstract Preservatives are common ingredients widely used in everyday products. Parabens are the most commonly used preservative in cosmetics and topical medications. The safety of parabens for use as a preservative in cosmetics has come into question; and thus consumer demand for paraben-free products is ever increasing. In this study Shimadzu Reversed phase High Performance Liquid Chromatography method developed for the separation of two paraben preservatives (methyl- and propyl parabens) using a Luna C18(2) column (5u, 250 mm x 4.6 mm) in 10 marketed cosmetics products. The separation was completed within 21 min where Methyl and Propyl Paraben Retention Time was around 14.6931 minutes and 20.4422 minutes respectively at a flow rate of 1 ml/min and a binary gradient mobile phase containing water and acetonitrile have been used in different proportions. The method was applied and validated satisfactorily for the determination of these parabens in commercial cosmetics samples. The levels of the two parabens determined in 8 cosmetic product samples were not in agreement with the European Union Cosmetic Directive (EU Cosmetics Directive 76/768/EEC).
Thesis
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Preservatives are common ingredients widely used in everyday products. Parabens are the most commonly used preservative in cosmetics and topical medications. The safety of parabens for use as a preservative in cosmetics has come into question; and thus consumer demand for paraben-free products is ever increasing. In this study Shimadzu Reversed phase High Performance Liquid Chromatography method developed for the separation of two paraben preservatives (methyl- and propyl parabens) using a Luna C18(2) column (5u, 250 mm x 4.6 mm) in 10 marketed cosmetics products. The separation was completed within 21 min where Methyl and Propyl Paraben Retention Time was around 14.6931 minutes and 20.4422 minutes respectively at a flow rate of 1 ml/min and a binary gradient mobile phase containing water and acetonitrile have been used in different proportions. The method was applied and validated satisfactorily for the determination of these parabens in commercial cosmetics samples. The levels of the two parabens determined in 8 cosmetic product samples were not in agreement with the European Union Cosmetic Directive (EU Cosmetics Directive 76/768/EEC).
Article
The oil palm (Elaeis guineensis) fruit is a source of vegetable oil and various phytonutrients. Phytochemical compounds present in palm oil include tocotrienols, carotenoids, phytosterols, squalene, coenzyme Q10, and phospholipids. Being a fruit, the oil palm is also a rich source of water-soluble phytonutrients, including phenolic compounds. Extraction of phytonutrients from the oil palm vegetation liquor of palm oil milling results in a phenolic acid-rich fraction termed Water-Soluble Palm Fruit Extract (WSPFE). Pre-clinical in vitro, ex vivo, and in vivo studies carried out using various biological models have shown that WSPFE has beneficial bioactive properties, while clinical studies in healthy volunteers showed that it is safe for human consumption and confers antioxidant and anti-inflammatory effects. The composition, biological properties, and relevant molecular mechanisms of WSPFE discovered thus far are discussed in the present review, with a view to offer future research perspectives on WSPFE for health and non-health applications.
Article
Parabens are used as a preservative in several consumer products including cosmetics, personal care products, and medicinal products. These chemicals have been suspected for estrogenicity and potential adverse endocrine outcomes in humans. For the first time, exposure profiles and potential sources of major parabens are investigated for a nationally representative population of children and adolescents of Korea. In addition, major determinants of urinary paraben levels were identified. For this purpose, the children, and adolescents (n = 2355, 3–18 years of age) who participated in the Korean National Environmental Health Survey cycle 3 (2015–2017) were studied. Adjusted multiple linear regression models were employed to investigate the relationships of several potential demographic and behavioral determinants of exposure, with the urinary levels of three parabens; methyl, ethyl, and propyl paraben. Methyl and propyl paraben levels of the Korean children and adolescents were comparable to those of the US, but the high exposure group (95th percentile) showed much higher levels of exposure. Moreover, urinary ethyl paraben levels are always higher than those of other countries. The uses of personal care products including liquid soaps, fragrance products, nail polish, or antiseptic products were significantly associated with urinary paraben levels. In addition, dietary sources such as fast food and canned food consumption were identified as major contributors to ethyl paraben levels. For methyl and propyl parabens, the use of fever medications and ointments were identified as major determinants of the exposure, especially among the younger children of 3–5 years of age. These observations are related to the Korean regulations that permit the use of the parabens as preservatives in foods and medications. The findings demonstrate that the exposure profile of parabens among Korean children are unique, and mitigation efforts for some parabens are required in Korea. Further studies are warranted to confirm the exposure sources of parabens and to develop mitigation measures among Korean children and adolescents.
Article
An effective and fast vortex-assisted dispersive liquid–liquid extraction method was developed for the extraction of paraben in cosmetic samples and water samples. The paraben was determined and quantified using ultraviolet-visible (UV-Vis) spectrometry. A response surface methodology (RSM) based on the central composite design was used for the optimization of factors (composition of the extractant, volume of extractant, extraction time, centrifugation time, and centrifugation velocity) affecting the extraction efficiency of the procedure. The optimum parameters for vortexassisted dispersive liquid–liquid extraction (VA-DLLE) are: chloroform used as the extractant solvent, 5 ml volume of extractant, 3 min extraction time, 5 min centrifugation time, and 2400 rpm centrifugation velocity. The limit of detection (LOD) and the limit of quantification (LOQ) for paraben are 0.0476 and 0.1442 μg/mL, respectively. Spiked cosmetic samples have the extraction recoveries in the range of 81.2–96.8%, whereas spiked water sample extraction recoveries were in the range of 88.8–100.63%. Each sample was repeated (n = 2), with a relative standard deviation of <5.74% for cosmetic samples and <9.03% for water samples. In conclusion, this extraction method is fast and inexpensive for the extraction of paraben.
Article
Background Parabens are esters of p-hydroxybenzoic acid and are widely used as preservatives in cosmetics, pharmaceuticals and foodstuffs. The presences of parabens in infant formulas raise concerns due to their potential to disrupt endocrine function in infants and cause reproductive toxicities.Methods In this study a new method was developed for extraction and determination of methylparaben in infant formulas using HPLC method and UV detector. Methanol and trichloroacetic acid were used for extraction and isocratic mobile phase comprising equal proportions of glacial acetic acid in water (50:850 v/v) and methanol was used for separation of methylparaben.ResultsRecovery of the extraction procedure was good and interferences between methylparaben and other ingredients peaks in HPLC chromatograms decreased. The average recoveries for methylparaben were about 88–108 %. The limit of detection and limit of quantitation for methylparaben were 0.2 and 0.5 µg/mL, respectively. Results of the method showed good reproducibility (relative standard deviation (RSD) 0.29–1.94 % for within day analysis and 0.84–2.18 % for between day analysis). Results were linear in range of 0.5–20 µg/mL methylparaben. The results of twenty real infant formula samples showed methylparaben was found only in one sample in concentration 0.3 µg/mL.Conclusions The new extraction and measurement method was a short-time method and could be applicable for large numbers of samples. This method was fast, sensitive and accurate and was capable of being used in legal laboratory references for determination of methylparaben content.
Article
Ethylparaben (EtP) and propylparaben (PrP) are common preservatives and well-known endocrine-disrupting chemicals. Studies have demonstrated that they can reduce female fertility, but the underlying mechanism, especially that on embryo implantation, is still poorly understood. Endometrial decidualization is a critical event for embryo implantation. In this study, we aimed to explore the effects of EtP/PrP on endometrial decidualization. Pregnant mice were dosed daily by oral gavage with EtP at 0, 400, 800 and 1600 mg/kg or with PrP at 0, 625, 1250 and 2500 mg/kg from Day 1 of pregnancy until sacrifice. The results showed that the rate of pregnant mice with impaired embryo implantation, whose number of implantation sites was less than 7, was significantly increased after exposure to 1600 mg/kg EtP or 2500 mg/kg PrP. Further study found that the expression of endometrial decidualization markers HOXA10, MMP9 and PR was significantly downregulated in 1600 mg/kg EtP group and 2500 mg/kg PrP group. Notably, serum oestrogen and progesterone levels were significantly increased, whereas the expression of uterine oestrogen receptor and progesterone receptor was decreased following 1600 mg/kg EtP or 2500 mg/kg PrP exposure. In the breeding test, fewer offspring were found after females were exposed to 1600 mg/kg EtP or 2500 mg/kg PrP in early pregnancy. This demonstrated that exposure to EtP/PrP interfered with embryo implantation by compromising endometrial decidualization in early-stage pregnant mice. Disorders of reproductive hormones and hormone receptor signals could be responsible for impaired decidualization. This study broadened the understanding on the biological safety of EtP and PrP.
Chapter
Pharmaceuticals and personal care products (PPCPs) include therapeutic drugs, fragrances, sunscreens, detergents, cosmetics, plasticizers, and their metabolites. Presence of these compounds at detectable levels in the environment (surface, ground and wastewater, effluents, soil, and sediment) poses a threat to living biota. Humans get exposed to these compounds via consumption of contaminated food/water and through external application. These compounds break down and get transformed into secondary compounds that have harmful effects on human health. Many of these compounds act as endocrine disrupters and target specific metabolic, molecular pathways in humans. They prove toxic and induce neurological, biochemical, and physiological defects. They act as causal agents of diseases such as cancer, diabetes, bronchitis, respiratory tract infection, teratogenic disorders, and reproductive disorders in humans. Dioxin compounds in particular affect brain development and produce developmental defects in children. Study of the mode of action of PPCPs can prove useful in finding ways of minimizing their toxicity.
Article
Isolated hepatocytes from male rats were cultured in primary cell culture in 24-well dishes for 20-24 hours in the presence of the various test compounds. Cytotoxicity at the end of the culture period was evaluated by the determination of LDH-release into the culture medium or by quantification of DNA content as a measure of the cell number in each well. Toxic xenobiotics, such as chlorpromazine, were able to induce LDH-release at up to 5 times the background levels at concentrations of 10-4-10-5M. For most compounds, the increase in LDH-release was closely related to a decrease in cell number, as measured by the DNA method. Two culture conditions which might influence the cytotoxic response were investigated. Prolongation of the culture time increased the toxicity of some compounds, e.g. sodium dodecylsulphate, whereas for other compounds, e.g. amitriptyline, no change was noted. Addition of serum albumin and a1-acid glycoprotein decreased the toxicity of chlorpromazine to isolated hepatocytes. These results indicate that isolated hepatocytes might represent a useful in vitro toxicity screening system, and that careful standardisation of the culture conditions is necessary.
Article
A 47-year-old woman complained of itchy erythema on her face that occurred soon after contact with the cosmetics and edema of her lips when she used dentifrices. Closed patch tests for 15 minutes with the cosmetics, schampoo and dentifrice showed marked wheal and flare reaction. Patch test reaction to each ingredient of these products was positive only to methylparaben. Cross-reaction with paraben, ethylparaben, propylparaben, butylparaben, methylsalicylate and acetylsalicylic acid was not observed.
Article
One hundred patients suspected to be having contact hypersensitivity to topical medicaments were patch tested with methly and propyl parabens along with commercially available topical medicaments. Six patients showed positive reactions to parabens. Two patients each were positive to methyl paraben and propyl paraben and two showed positive reactions to both of these. Three patients each showed positive reactions to soframycin, econazole and nitrofurazone also.
Article
Undesirable reactions to local anesthetics occur in 2-3 % after their administration, but real allergic reactions appear in less than 1 % of all undesirable reactions, predominantly to anesthetics in the group of esters. Careful history and incremental challenge test using a local anesthetic usually can distinguish the true allergic reaction from other side effects. Only one case of allergy to local anesthetics was proved in the group of 15 patients examined by exposure test.
Article
The Parabens are esters of p-hydroxybenzoic acid (PHBA) and are the most commonly used as preservatives in cosmetic formulations. Data obtained from chronic administration studies indicate that Parabens are rapidly absorbed, metabolized, and excreted. Acute chronic and subchronic toxicity studies in animals indicate that Parabens are practically nontoxic by various routes of administration. Methylparaben and Ethylparaben at 100 percent concentration were slightly irritating when instilled into the eyes of rabbits. Numerous in vitro mutagenicity studies indicate that the Parabens are non-mutagenic. Methylparaben was noncarcinogenic when injected in rodents or when administered intravaginally in rats. Cocarcinogenesis studies on Propyl- and Methylparaben were negative. Teratogenic studies on Methyl- and Ethylparaben were also negative. Parabens are practically nonirritating and nonsensitizing in the human population with normal skin. Paraben sensitization has been reported when Paraben-containing medicaments have been applied to damaged or broken skin. Photo-contact sensitization and phototoxicity tests on product formations of Methyl-, Propyl-, and/or Butylparaben gave no evidence of significant photoreactivity. It is concluded that Methylparaben, Ethylparaben, Propylparaben, and Butylparaben are safe as cosmetic ingredients in the present practices of use.
Article
The cytotoxicities of 50 coded chemicals from the FRAME blind trial set were estimated by the FRAME kenacid blue (KB) and Rockefeller neutral red (NR) assay methods after test periods of 24 hours and 72 hours with murine 3T3 fibroblasts. Results obtained after the two test periods were considered to be similar for 25 of the chemicals, but different for 25 others. Our results indicate that a test period of 72 hours is more suitable for the assessment of potential cytotoxicity by the KB and NR methods than the 24 hour test period, which is less likely to allow sufficient time for certain chemicals to exert their toxic effects, particularly those that inhibit cell division or affect cell viability through other long-term effects. A comparison of results obtained by the 72 hour KB method with 3T3 cells and with human BCL-D1 cells indicated that substantially different ID50 values were found for 8 of 48 chemicals. These results are discussed in terms of the importance of choice of test period, assay method and cell type used in in vitro cytotoxicity tests.
Article
The minimum inhibitory concentrations (MICs) of methyl phydroxybenzoate (methyl paraben) and potassium sorbate for four psychrotrophic bacteria were compared at pH 5 and 6 and at 5 and 30°C. The bacteria tested were Listeria monocytogenes, Pseudomonas putida, Yersinia enterocolitica, and Aeromonas hydrophila. L. monocytogenes was generally the most resistant and A. hydrophila the least resistant to the preservatives. The differences between the bacteria were substantial. The MICs of the two preservatives were similar at pH 5, but at pH 6 the MICs of paraben were well below those of sorbate, except in the case of A. hydrophila. The MICs at 5°C were much lower than those observed at 30°C for all of the bacteria except P. putida. All four bacteria were inhibited by 1000 mg methyl paraben per L at 5°C. Exposure of the bacteria to concentrations of preservative that permitted growth at 30°C did not lead to adaptation to the preservative. The death rates of the bacteria in media containing 1000 mg methyl paraben per L varied over a wide range. At 5°C, a 3 log10 decrease in viable counts of L. monocytogenes and A. hydrophila took >4 months and a few days, respectively. Injury of L. monocytogenes, Y. enterocolitica, and A. hydrophila was detected under these conditions. Repair of the injury was demonstrated, with up to 24 h required for complete recovery. The type of buffer in which the test medium was prepared affected the preservative MICs and rate of injury of L. monocytogenes. Copyright ©, International Association ot Milk, Food and Environmental Sanitarians.
Article
The sensitivity of Listeria monocytogenes Scott A and ATCC 19114 to antimicrobial compounds was altered when bacterial membrane lipid composition was modified by growth in the presence of added fatty acids. Analysis of cellular fatty acid composition by gas-liquid chromatography indicated that L. monocytogenes Scott A cells contained 0.97, 2.32, 0.81, and 0.72% (relative) of C14:0, C16:0, C18:0, and C18:l, respectively. In the presence of exogenously supplied C14:0, C16:0, C18:0, and C18:l, the percentages increased to 14.03, 30.92, 16.30, and 27.90%. Average MICs for L. monocytogenes Scott A and ATCC 19114 to sodium chloride, tertiary butylhydroquinone, methyl paraben, and propyl paraben were 10.0%, 81, 1406, and 544 μg/ml, respectively. Growing either strain in the presence of 50 μg/ml of either exogenously added C14:0 or C18:0 fatty acids increased their resistance to the four antimicrobial compounds. However, growth in the presence of C18:1 led to increased sensitivity to the antimicrobial agents. The results indicate that the susceptibility of L. monocytogenes to antimicrobial agents is related to the lipid composition of the cell membrane. Consequently, food preservation processes which alter fatty acid composition of L. monocytogenes could result in changes in antimicrobial susceptibility.
Article
Various nasal formulations have been tested for their suitability to deliver drugs through the nasal cavity. This route is especially of interest where the dose of drug is small and the drug may undergo an extensive first-pass metabolism and/or decomposition while passing through the gastrointestinal tract. Unfortunately, the nasal mucosa does not have same type of tolerability to all drugs and additives used in formulations. Some chemicals may damage the nasal epithelia or alter the mucociliary defensive mechanism of the nose. There also is a possibility that the drug can transport directly from nasal cavity to the brain via the olfactory route. Several methods have been developed to study the impact of drugs and excipients on the integrity of the nose. In some cases, the in vitro results did not correlate well with in vivo data, due to lack of reproducibility of the natural body environment, and some in vitro methods may not be sensitive enough and thus may complicate interpretation of the results. This...
Article
One hundred patients suspected of having allergic eczematous contact dermatitis due to topically administered medications were patch tested with a "vehicle tray" composed of 15 substances commonly found in vehicles of current preparations. Positive tests were obtained in 30 of 100 patients. There were 18 reactions to ethylenediamine; 6 to lanolin; 3 to parabens; 2 each to phenylmercuric acetate, thimerosal, dichlorophene, propylene glycol monostearate, and triethanolamine; 1 to sorbic acid for a total of 40 positive reactions. Vehicles play a significant role in producing sensitization and allergic contact dermatitis. The importance of testing with a standard concentration of each ingredient in preference to the total formulation is shown by the sizable incidence of false-negative reactions with the total formulation.
Article
information was erroneous in 9 cases (10.2%). When the moisturmanufacturers/suppliers. The moisturizers were not necessarily freshly izers were investigated for the presence of the 9 preservatives prepared, but still far from the expired date. The products were kept which should not be present in the moisturizers according to the at room temperature during the time of investigation. These moisturmanufacturers/suppliers, at least one of the preservatives was izers are well-known and common on the Swedish market and were detected in 17 moisturizers (17.0%). selected to represent manufacturers from different geographical areas Parabens were the most common preservatives. The concentra- and moisturizers to be used in the face, on the body and the hands. tions of the 9 preservatives did not exceed the maximum During the investigation period there were no signs of deterioration concentrations allowed in cosmetics. of any moisturizer. However, no chemical investigations of the stability When a patient with suspected allergic contact dermatitis tests of the preservatives were carried out. positively to a preservative, the assessment of present clinical Reference substances relevance requires demonstration of exposure to the The preservatives were obtained from various suppliers ( Table I ). sensitizer.This demonstration cannot rely solely on information Usually a mixture of parabens is used, as a preservative and the on the packages or from the manufacturers/suppliers but has separate parabens are not always specified. In this study methyl, ethyl, allergic contact dermatitis; formaldehyde releasers; high- Kathon CG, consisting of 1.125% MCI and 0.375% MI, was used performance liquid chromatography; methylchloroisothiazoli- when standard solutions of MCl/MI were prepared.
Article
We reexamined safety of some cosmetic materials on a hereditary toxicity. The cosmetic materials tested were preservatives, Sunscreens, antioxidants, hormones and surfactants. Mutagenicity assay were carried out for Rec-assay using Wild and Recombination-deficient strains of B. Subutilis and Reversion assay using Salmonella typhimurium TA98 and TA100 with or without the microsomal activation (±S-9mix). In addition to the above-described procedures, Rec-assay with irradiating fluorescent lump or cold incubation were carried out to some materials, such as sunscreens and antioxidants. Irg-DP300, a preservative, was weak rec-positive at very high concentration such as 5 mg/ disk, but negative on revession assay. Both 8-MOP and 0-201 newly found out as positive control of photo-rec assay were clearly rec-positive by irradiation of fluorescent lump, but all of sunscreens and antioxidants were negative. Estradiol, a hormone, induced slightly more revertants than control with S-9mix and three anion surfactants of sulfate derivatives (Surf-1, 2, 4) and two nonion surfactants of cetyl ether and lanolin alcohol derivatives (Surf-13, 14) also exhibited the same effects with or without S-9mix, but we couldn't sufficiently recognize these mutagenicity. These phenomena are yet obscure whether due to any reasons.
Article
Seven patients with allergic vascular purpura displayed hypersensitivity reactions after ingestion of azo dyes and benzoic acid compounds. All reacted with purpura after oral provocation with azo dyes. Three patients also developed purpura after ingesting benzoic acid compounds and four developed purpura after taking aspirin. Mild purpuric reactions after provocation are more easily revealed if the skin is pretreated with a nicotinic acid ester. The patients improved on a diet free from the additives. Beneficial effects, with decreased purpuric reactions after provocation, have also been observed from treatment with phenformin and ethylestrenol.
Article
The development of Candida albicans infection, or moniliasis, following antibiotic therapy has received considerable attention recently. The true incidence of this condition, however, is debatable. Lipnik, Kligman, and Strauss1 have reviewed the subject in an attempt to define the possible role that C. albicans may play in the production of side reactions to antibiotics. They concluded that true moniliasis is very rare in people treated with antibiotics and that the mere presence of the organism in the oral cavity or in the gastrointestinal tract does not justify a diagnosis of C. albicans infection. Having treated hundreds of patients with wide-spectrum antibiotics in this clinic we are of the same opinion. Our evidence suggests that yeast-like organisms may be found in varying numbers in the intestinal tract as part of its normal flora (presumably true for the oral flora, too) in a large percentage of untreated persons, provided adequate isolation
Article
A hydrocortisone preparation containing methylparaben and propylparaben provoked bronchospasm and pruritis when given intravenously to an asthmatic patient, whereas another hydrocortisone preparation without paraben preservative did not. Direct and passive transfer (Prausnitz-Küstner) skin tests for immediate hypersensitivity to parabens were positive. Parabens, frequently employed as bacteriostatic agents, are capable of producing immunologically mediated, immediate systemic hypersensitivity reactions.(JAMA 237:1594-1595, 1977)
Article
To the Editor.— Parabens are a relatively rare cause of allergic contact dermatitis. However, sensitivity to these compounds is of extreme importance because of their widespread use as preservatives in topical and systemic medications. To our knowledge, there has been no previous report of systemic eczematous contact dermatitis due to parabens. Case Report.— A 35-year-old man was recently seen at the Dermatology Clinic, Fitzsimons Army Medical Center, with a mild eczematous dermatitis involving the face, neck, upper extremities, and groin. The patient has been using 0.1% triamcinolone acetonide, 100,000 units/gm nystatin, 0.25% neomycin, and 0.25% gramicidin (Mycolog cream) for ten days prior to his initial visit. An allergic contact dermatitis was suspected and he was treated with triamcinolone acetonide, 0.1% (Kenalog spray) and was patch tested to the standard screening antigens as proposed by the International Contact Dermatitis Research Group. This series contains the common antigens in Mycolog, including neomycin
Article
The initial rates of kill of Escherichia coli by methyl, ethyl and propyl parabens are similar at equal saturation fraction in a buffered salts-glucose medium. This is as expected from the Ferguson principle of equal activity of homologs, but the survival curves soon diverge strongly, apparently because the rate of adaptation increases markedly with increasing molecular weight; E. coli adapts readily to propyl paraben, hardly at all to methyl. As a result, the parabens clearly rank methyl > ethyl > propyl > butyl > benzyl in their antimicrobial capacities at equal saturation fraction. The same ranking holds when equal weight concentrations are challenged with other bacteria in oil/water emulsions and in a shampoo base. Performance in these systems is discussed in terms of apparent solubilities. Mixtures of parabens are not superior except when multiple saturation is possible. In overall performance, only methyl paraben appears to be a good preservative.
Article
The frequency of positive reactions to 5-chloro-2-methyl-4-isothiazolin-3-one (MCI/MI) were studied at 22 European cntact dermatitis clinics over a period of 1 year. A total of 4713 patients participated. All the patients were patch tested with nickel sulphate, formaldehyde, paraben-mix, and MCI/MI 19.4% of the patients had positive patch tests to nickel, making this the most common allergen, 3% of the patients reacted to 100 ppm MCI/MI, while 2.6% reacted to formaldchyde and 1.1% to parabens. There was great variation in the frequency of MCI/MI sensitivity among the 22 centres. MCI/MI contact allergy was most common among women and in patients with facial dermatitis, while it was rarely seen in patients with dermatitis on the lower legs. There were no fluctuations in the number of positive patch tests to MCI/MI on a monthly basis when the results from all centres were combined. 117 of the 141 MCI/MI sensitized patients included in the study were retested 88% had positive patch tests when retested. 101 of the MCI/MI-sensitive patients participated in a double -blind, placebo-controlled product use test. This test showed that 31% of the MCI/MI-sensitive patients had a positive reaction to a MCI/MI-preserved product. Only a few patients reacted to a control product. It is concluded that the preservative MCI/MI is an important new contact allergen.