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Final Report on the Safety Assessment of Methylparaben, Ethylparaben, Propylparaben, and Butylparaben
Abstract
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.
... Both methylparaben as well as green tea extract showed higher thermal resistance compared to the essential oil and rosemary extract. In the case of OO and RE, a significant loss of mass occurred at a temperature of about 230-250 • C, which is above the processing temperature described in the literature [31,32]. Due to high weight loss of the rosemary extract and oregano oil samples (100 and ca. ...
... This loss may also be attributed to the volatilization/decomposition of bioactive compounds from the substances, e.g., for rosemary extract, possibly decomposition off phenolic diterpenes, such as carnosic acid and carnosol, as well as rosmarinic acid. For green tea extract, oregano oil and rosemary extract, the third step-small mass loss-can be related to inorganic compounds [23,25,[31][32][33][34]. ...
... Both methylparaben as well as green tea extract showed higher thermal resistance compared to the essential oil and rosemary extract. In the case of OO and RE, a significant loss of mass occurred at a temperature of about 230-250°C, which is above the processing temperature described in the literature [31][32]. Due to high weight loss of the rosemary extract and oregano oil samples (100 and ca. ...
Bioactive polypropylene (PP) films with active agents) presence for food packaging application have been prepared and characterized. The novel modified PP films were obtained via PP/additives systems regranulation and cast extrusion. The influence of two types of plasticizers (natural agents as well as commercial synthetic product) and bioactive additives on final features, e.g., mechanical properties, was evaluated. Moreover, the biocidal activity of the films was determined. Due to their functional properties, they are developed as additives to packaging plastic materials such as polyolefins. The study results presented in our work may indirectly contribute to environmental protection by reducing food waste. The aim of the work was to obtain innovative, functional packaging materials with an ability to prolong the shelf life of food products. The best antimicrobial properties were observed for the sample based on 5 wt.% oregano oil (OO) and 5 wt.% cedar oil (OC) in PP matrix. A microbial test revealed that the system causes total reduction in the following microorganisms: B. subtilis, E. coli, S. aureus, P. putida, C. albicans, A. alternata, F. oxysporum.
... Elder et al. [37] reviewed several studies about human skin irritation for products with parabens at 0.1-0.8%. In general, no irritation was noticed, although some cases of moderate irritation were reported. ...
... The major studies involving PP did not show significant problems or statistically significant results for wellstructured and well-defined conclusions in animals, including for carcinogenic and reproduction tests. However, some studies for products containing MP, EP, PP and BuP at 0.1-0.8% were carried out by Elder et al. [37], and some products caused slightly or minimal eye irritation in rabbits [22]. Additionally, the application of PP at 10% caused irritation when applied to rabbit skin [22]. ...
... Soni et al. [21] reviewed studies using methylparaben for oral, dermal, and intrathecal short-term effects, and concluded that no data or conclusions could prove toxicity effects in rats for oral or intrathecal exposition. However, a group of rabbits where dermal toxicity was studied showed moderate and well-defined erythema, slight edema, and slight desquamation, using products containing 0.2% of MP applied for 3 months daily at doses of 5.5 mg/cm 2 /8.4% body surface area [21,37]. For another study using the same percentage of MP and dose of 6.6 and 11 mg/cm 2 /8.4%, the same occurred, and in another study of 0.2% of MP and PP in rabbits for doses of 2 and 6 mg/cm 2 /10% of area, the product caused moderate erythema, slight edema, and mild desquamation, and, occasionally, some epidermal fissures with bleeding and papuloerythema [21]. ...
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.
... Parabens are quickly absorbed from the blood and gastrointestinal tract, hydrolyzed to 4-Hydoxybenzoic Acid, conjugated, and the conjugate excreted in the urine. 46 Data obtained from chronic administration studies indicate that parabens do not accumulate in the body. Serum concentrations of parabens, even after intravenous administration, quickly decline and remain low. ...
... Acute toxicity studies in animals indicate that parabens are practically nontoxic by various routes of administration. 46 1986. Benzylparaben was not considered an acute toxic agent to mice or rats. ...
... Subchronic oral studies indicate that parabens are practically nontoxic. 46 A subchronic oral toxicity study in humans indicated that Methylparaben was practically nontoxic at doses up to 2 g/kg/d. ...
The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 21 parabens as preservatives in cosmetic products. All of these ingredients are reported to function in cosmetics as preservatives; however, 5 are reported to also function as fragrance ingredients. The Panel reviewed relevant data relating to the safety of these ingredients under the reported conditions of use in cosmetic formulations. The Panel concluded that 20 of the 21 parabens included in this report are safe in cosmetics in the present practices of use and concentration described in this safety assessment when the sum of the total parabens in any given formulation does not exceed 0.8%. However, the available data are insufficient to support a conclusion of safety for benzylparaben in cosmetics.
... Parabens are low-cost, broad-spectrum antimicrobial agents in personal care products, food and pharmaceuticals (Elder, 1984;Ana and Paula, 2016). Methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP) are p-hydroxybenzoic acid esters with alkyl substituents of increasing length (Andersen, 2008). ...
... Methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP) are p-hydroxybenzoic acid esters with alkyl substituents of increasing length (Andersen, 2008). It has been suggested, that the widespread use of parabens (Elder, 1984;Kim and Chevrier, 2020) may contribute to the global metabolic and cardiovascular health epidemic due to potential endocrine disrupting properties (Heindel et al., 2015;Heindel and Blumberg, 2019). There are conflicting results in studies investigating links with metabolic outcomes (Kim and Chevrier, 2020;Reimann et al., 2021;Lee et al., 2019;Pazos et al., 2019;Quirós-Alcalá et al., 2018;Hu et al., 2013;Liu et al., 2019a), and parabens' general classification of potential cardiometabolic effects remains challenging. ...
Background and aim:
Parabens are widely used as antimicrobial preservatives in personal care products. Studies investigating obesogenic or cardiovascular effects of parabens show discordant results, while data on preschool children are lacking. Paraben exposure during early childhood could have profound cardiometabolic effects later in life.
Methods:
In this cross-sectional study paraben concentrations [methyl (MeP), ethyl (EtP), propyl (PrP), butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 300 urinary samples of 4-6-year-old children of the ENVIRONAGE birth cohort. Paraben values below the limit of quantitation (LOQ) were imputed by censored likelihood multiple imputation. The associations between log-transformed paraben values and cardiometabolic measurements (BMI z-scores, waist circumference, blood pressure and retinal microvasculature) were analyzed in multiple linear regression models with a priori selected covariates. Effect modification by sex was investigated by including interaction terms.
Results:
Geometric means (geometric SD) of urinary MeP, EtP, and PrP levels above the LOQ were 32.60 (6.64), 1.26 (3.45), and 4.82 (4.11) μg/L, respectively. For BuP more than 96% of all measurements were below the LOQ. Regarding the microvasculature, we found direct associations between MeP and central retinal venular equivalent (β = 1.23, p = 0.039) and PrP with the retinal tortuosity index (β = 0.0018, p = 0.0044). Furthermore, we identified inverse associations between MeP and ∑parabens with BMI z-scores (β = -0.067, p = 0.015 and β = -0.070, p = 0.014 respectively), and EtP with mean arterial pressure (β = -0.69, p = 0.048). The direction of association between EtP and BMI z-scores showed evidence for sex-specific differences with a direct trend in boys (β = 0.10, p = 0.060).
Conclusions:
Already at young age paraben exposure is associated with potentially adverse changes in the retinal microvasculature.
... Among all the substances used as preservative agents, the group of esters of p-hydroxybenzoic acid also known as parabens is the spearhead since the 1920 s. [1,2] For the time being, it is demonstrable that parabens are universally present in an enormous diversity of commodities including food, cosmetics, personal care products, drinks, packing supplies and materials, cigarettes, animal feed etc. Parabens are also present as common ingredients in pharmaceuticals as excipients contributing to the avoidance of any contamination and to the prevention of the degradation of the drastic substance. Focusing only on cosmetics, parabens exist at least in 22,000 products. ...
... Some useful information and physicochemical characteristics for selected parabens are listed in Table 1. [1][2][3][4][5][6][7][8] In the human body, parabens pass from the gastrointestinal tract into the blood, where they can be metabolized to PHBA, which is excreted through the urinary system as free form or conjugated. Moreover, the enzymes named carboxylesterases, which exist in skin, in other subcutaneous tissues and in organs affiliated with the metabolic system (liver), transact fluctuating hydrolysis of parabens. ...
Sample preparation and extraction of the analytes are the cornerstones of any bioanalytical method, exerting profound influence on the entire procedure. Herein is presented an overview of sample pretreatment and extraction approaches of the esters of p-hydroxybenzoic acid also known as parabens, from human biological matrices prior to liquid chromatography analysis. Parabens are homologues chemicals compounds that are omnipresent as preservatives in products of daily use due to their efficient antimicrobial activity. However, parabens demonstrate estrogenic activity and thus are endocrine disrupting chemicals, involved in the deregulation of the hormone system and connected with the incidence of human breast cancer and other health malfunctions and disease processes. Consequently, the determination of parabens in human biological samples, which is a challenging task due to the matrix complexity, is a matter of great interest for epidemiological and toxicological purposes. Matrix complexity and interferences may be avoided by adopting an appropriate extraction protocol. Thus, this review focused on efficient previous reported sample pretreatment and extraction protocols coupled with liquid chromatography, which is the most prevalent analytical technique.
... Parabens are the alkyl esters of 4-hydroxybenzoic acid and generally classified into seven different types (methyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl-, and benzyl-paraben) depending on the positioning of the different ester groups at C-4 position, and longer ester groups are known to have greater antimicrobial potential as well as toxicity (Elder, 1984;Soni et al., 2005), while shorter alkyl chains are also known to have relatively faster degradation rate compared to the longer ones. Due to properties (effective antimicrobial activity, safety, and sufficient solubility in water) of parabens, they were used as antimicrobial preservatives from 1920s and its usage has been consistently increased in a variety of products such as cosmetics, food, and pharmaceuticals to prevent microorganismmediated decomposition (Sabalitschka, 1930;Soni et al., 2005). ...
... There are the reports on the safety of paraben (Elder, 1984;Andersen, 1995) but recently adverse effects of parabens have been highlighted. For example, in 20 human breast tumors, high concentrations of parabens (20.6 ± 4.2 ng/g tissue) have been found with the highest concentration of MeP (2.8 ± 2.2 ng /g tissue), suggesting that bioaccumulation of paraben is highly associated with carcinogenesis (Darbre et al., 2004). ...
Parabens are used as a preservative substance in a wide range of man-made products causing deleterious effects on aquatic organisms and therefore, the concern of their effects to aquatic organisms has been increased. In this study, acute toxicity of methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP) was assessed in the marine copepod Tigriopus japonicus. The acute toxicity assessment resulted in the median lethal concentration (LC50) values of MeP, EtP, and PrP were 29754, 11659, and 113 μg/L, respectively, for male and 38183, 15371, and 357 μg/L, respectively, for female, indicating the strongest toxicity of PrP, compared to MeP and EtP and the higher sensitivity of males compared to females. Developmental retardation and reproduction rate were also measured under chronic exposure. Furthermore, significant alteration in sex ratio was shown in PrP-exposed group, indicating PrP would have feminization effect in T. japonicus. Here we report different toxicity of three types of parabens and also shows potential estrogenic effects of PrP in T. japonicus.
... Earlier, it was concluded that Methylparaben, Ethylparaben, Propylparaben and Butylparaben are safe as cosmetic ingredients in the present practices of use. [37] The Cosmetic Ingredient Review (CIR) Expert Panel concludes that the available data are insufficient to support the safety of Benzylparaben as used in cosmetics. [6] However, Parabens were implicated in numerous cases of contact sensitivity associated with cutaneous exposure; reported to cause contact dermatitis reactions in some individuals on cutaneous exposure but the mechanism of this sensitivity is unknown. ...
... [69] Seventy years of use have confirmed the excellent safety of Parabens asstable, effective and nonirritant preservatives. [21,37,70] In 1940, Bonnevie in Denmark described the first case of allergic contact dermatitis from Parabens. [28,71] Allergic dermatitis, eczema is, therefore, often difficult to diagnose, presenting as recalcitrant dermatitis that fails to improve or worsens under seemingly adequate treatment. ...
Parabens
were reported to cause contact dermatitis reactions in
some individuals on cutaneous exposure. Parabens have
been implicated in numerous cases of contact sensitivity
related to cutaneous exposure; endocrine disruption and
marine animal toxicity
... Parabens include methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), benzylparaben (BeP), and other esters of p-hydroxybenzoic acid, which are mostly used as preservatives in food, personal care products, and medicines because of their low reactivity, broad spectrum of antimicrobial activities, high chemical stability (with wide temperature and pH ranges), lack of odor, colorlessness, non-volatility, and low cost of production [1]. Parabens were previously considered safe, until it was reported that these chemicals may be related to breast cancer [2]. ...
Butyl paraben (BuP) has been widely used as a preservative in the cosmetics, food, and medicine industries. Recently, it has become a new pollutant and has attracted much attention. In order to evaluate the toxic effect of BuP on aquatic animals, Chinese striped-neck turtles (Mauremys sinensis) were exposed to BuP solutions with different concentrations of 0, 5, 50, 500, and 5000 µg/L for 20 weeks. The results showed that with an increase in BuP concentration, the activity of antioxidant enzymes (SOD, CAT and GSH-PX) in liver decreased. The expression of key genes in the Nrf2-Keap1 signal pathways first increased and then decreased, while the expression of the HSP70 and HSP90 genes increased. In addition, the liver had an inflammatory reaction. The expression of the BAFF and IL-6 genes increased and then decreased with an increase in BuP concentration, while the expression of P50 and P65 increased significantly. Oxidative stress induced apoptosis, and the expression of pro-apoptosis genes (BAX, cytc, Caspase3 and Caspase9) increased, while the expression of the anti-apoptosis gene Bcl2 decreased. The results provide an important reference for the comprehensive ecological and health risk assessment of environmental BuP.
... Acute toxicity reports of LAS to aquatic organisms have been published [68]. The toxic antimicrobial agent used in cosmetics [69], 4-hydroxybenzoic acid propyl ester (propyl paraben) was detected in the river and wastewater samples. Parabens have been associated with the development of breast cancer [70], decreased secretion and function of testosterone [71] and endocrine disrupting activities [72]. ...
... PP displays broad antibacterial activity against molds, yeast, and bacteria, and is a highly effective preservative and fungicide for use in food and medicine. [1][2][3] The concentration range of PP as an antibacterial substance in food, medicine, and cosmetics is typically from 0.01% to 0.20% (w/v). 4 With the increasing use of PP in various fields, the ingestion of PP by humans is becoming an increasingly complex issue, and exposure and absorption levels will likely increase. ...
Background
N-propylparaben (PP), a type of paraben, is commonly used as a preservative or antibacterial agent in daily chemicals, medicine, food, cosmetics, feed, and various industrial preservatives. Although PP promotes the growth of human breast adenocarcinoma (MCF-7) cells by activating the human estrogen receptor (ER), the mechanism responsible for this type of programmed cell proliferation is poorly understood.
Objective
To clarify the effect of PP on cell metabolic function and the potential molecular mechanism of PP induced MCF-7 cell proliferation from a new perspective.
Methods
To use high-resolution mass spectrometry-based metabolomics combined with bioinformatics analysis to analyze the molecular mechanism.
Results
The results illustrated that differential endogenous compounds related to the effects of PP on cell metabolic functions were detected. PP was found to promote glycolysis in MCF-7 cells and enhance the tricarboxylic acid cycle (TCA cycle) in mitochondria, thus improving the energy supply to these tumor cells for metabolic function and promotion of rapid proliferation. Moreover, we found that PP promoted cell proliferation by affecting the mitogen-activated protein kinase (MAPK) signaling pathway of MCF-7 cells.
Conclusion
Our results revealed the molecular mechanism of low concentration PP promoting MCF-7 cell proliferation by activating ER.
... Parabens exert non-mutagenicity according to earlier studies (Elder, 1984). Nevertheless, the weakly estrogenic and antiandrogenic activities of parabens resulting in potentially adverse reproductive and developmental outcomes have raised increasing concern (Oishi, 2001(Oishi, , 2002Golden et al., 2005;Nowak et al., 2018;Sun et al., 2022). ...
Background:
Parabens, as suspected endocrine disruptors, are widely used in personal care products and pharmaceuticals. However, variability, predictors, and risk assessments of human exposure to parabens are not well characterized.
Objective:
To evaluate within-day variability, predictors, and risk assessments of exposure to parabens among Chinese adult men.
Methods:
We measured four parabens including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) in repeated urine samples from 850 Chinese adult men. We examined the variability by intraclass correlation coefficients (ICCs) and identified the predictors by multivariable linear mixed models. We assessed risks of paraben exposures based on the estimated daily intake (EDI).
Results:
The four parabens were detected in >76% of urinary samples. We observed fair to good to high reproducibility (ICCs: 0.71 to 0.86) for urinary paraben concentrations within one day. Use of facial cleanser was associated with higher four urinary paraben concentrations. Increasing age, taking medicine, intravenous injection, and interior decoration in the workplace were related to higher urinary concentrations of specific parabens. Smoking and drinking were associated with lower urinary concentrations of specific parabens. The maximum EDIs for the four parabens ranged from 13.76 to 848.68 μg/kg bw/day, and 0.9% of participants had the hazard quotient values > 1 driven by PrP exposure.
Conclusions:
Urinary paraben concentrations were less variable within one day. Several lifestyle characteristics including use of facial cleanser and pharmaceuticals may contribute to paraben exposures.
... They are low-cost, broadspectrum antimicrobial, and antiseptic preservatives with greater effectiveness against Gram-positive bacteria than Gram-negative bacteria. Therefore, parabens are widely used in cosmetics, personal-care products, and pharmaceuticals to suppress microbial growth and extend product shelf life [1][2][3]. Additional paraben exposure is linked to indoor air and dust, foodstuffs, and tap water [4]. ...
Parabens are alkyl esters of p-hydroxybenzoic acid that are commonly used in pharmaceutical and cosmetic products. Humans are exposed to parabens when they use these products and through diet. There are growing concerns that paraben exposure can adversely impact human health. The endocrine-disrupting and obesogenic properties of parabens have been observed in animal studies and in vitro, prompting the increase in population-based studies of paraben exposure and adiposity-related endpoints. In this review, we summarize epidemiological studies published between 2017 and 2022 that examined paraben exposure in utero, between birth and adolescence, and in adulthood, in relation to adiposity-related measures. Overall, these studies provide some evidence that suggests that paraben exposure, especially during critical development windows, is associated with adiposity-related measures. However, we have noted several limitations in these studies, including the predominance of cross-sectional studies, inconsistent sample collection procedures, and small sample sizes, which should be addressed in future studies.
... Although parabens are long considered safe for human health, epidemiological studies have reported significant associations between human exposure to some parabens and adverse health outcomes, such as endocrine-disrupting effects, reproduction, and development (Elder 1984;Boberg et al. 2010;Baker et al. 2020), for example, in a recent study conducted by Baker et al. (2020), who reported that MeP in meconium was related to preterm birth, decreased gestational age, newborn weight, maternal thyroid hormone dysfunction, and children with attention-deficit hyperactivity disorder (ADHD). The growing evidence of toxicities of these chemicals has led to the implementation of some regulations for their application in consumer products. ...
Parabens are extensively used as preservatives in consumer products. The widespread exposure of human to parabens has been associated with adverse health effects. In this study, six parabens were measured in 100 indoor dust collected from homes, university dormitories, and cosmetics stores in Nanjing, China. Concentrations of sum of six parabens (∑6parabens) in dust from homes, university dormitories, and cosmetics stores ranged from 13.1 to 4.22 × 10³, 102 to 3.03 × 10³, and 7.02 × 10³ to 3.41 × 10⁴ ng/g, respectively. The median concentrations of ∑6parabens in dust from cosmetics stores (1.5 × 10⁴ ng/g) were 1–2 orders of magnitude higher than those found in dust from homes (166 ng/g) and university dormitories (1.23 × 10³ ng/g) (p < 0.01). Methyl-, ethyl-, and propyl-parabens were the predominant compounds found in dust samples, and the sum concentrations of three compounds accounted for 71.9–99.6%, 93.1–99.6%, and 94.7–99.6% of ∑6parabens in dust from homes, university dormitories, and cosmetics stores, respectively. Significant positive correlations were found between methyl- and propyl-parabens concentrations in three types of dust (r = 0.789–0.909), indicating their coexistence in many consumer products. The estimated daily intake (EDI) of ∑6parabens for adults via dust ingestion was highest for employees in cosmetics stores (median: 4.6 ng/kg bw/day), followed by university students (0.56–0.64 ng/kg bw/day), and adults in homes (0.075–0.087 ng/kg bw/day). The result provides a better understanding of human exposure to parabens in different indoor environments, and more studies are needed to further investigate the occurrence and potential health risks of parabens in dust from various microenvironments.
... Paraben compounds and their metabolites are among endocrine-disrupting chemicals, which impair the generation, transfer, binding, and function of the natural hormones of the body (Jakopin 2021). Accordingly, the use of parabens in the European Union, especially in Denmark has been restricted (Elder 1984;Andersen et al. 2007). These compounds are also toxic to aquaculture (e.g., fishes), daphnia, and algae (Bergfeld et al. 2005). ...
The current work is documented as the first record of the characteristics, removal efficiency, partitioning behavior, fate, and eco-toxicological effects of paraben congeners in a municipal wastewater treatment plant (WWTP, stabilization ponds) and hospital WWTPs (septic tank and activated sludge), as well as seawater-sediments collected from runoff estuarine stations (RES) and coastal stations (CS) of the north of the Persian Gulf. The median values of Σparabens at the raw wastewater and effluent of the studied WWTPs were 1884 ng/L and 468 ng/L, respectively. The activated sludge system had a greater removal efficiency (56.10%) in removing ∑parabens than the septic tank (45.05%) and stabilization pond (35.54%). The discharge rates of methyl paraben (MeP) was computed to be 2.23, 21.18, and 9.12 g/d/1000 people for stabilization ponds, septic tank, and activated sludge, respectively. Median concentrations of Σparabens in seawater (103.42 ng/L) and sediments (322.05 ng/g dw) from RES stations were significantly larger than from CS stations (61.2 and 262.0 ng/g dw in seawater and sediments, respectively) (P < 0.05). The median of field-based koc for Σparabens was 130.81 cm³/g in RES stations and 189.51 cm³/g in CS stations. It was observed that the concentration of parabens could have negative impacts on some living aquatic populations (invertebrates and bacteria), but the risk was not significant for fishes and algae.
Graphical abstract
... This hydrogel was designed to treat skin cosmetic affections such as acne scars. Restauder ® contains, among other additives, parabens as antibacterials [46,47], glycerin as plastificant [29], carbomer to control the consistency [48], propanediol to confer a non-sticky feel, and triethanolamine to stabilize the product. These compounds do not contribute to the wound-healing process, but they are widely used in cosmetics and personal care products. ...
Wound healing is fundamental to restore the tissue integrity. A topical study of the influence of Aloe vera hydrogel, formulated with 1,2-propanediol (propanediol) and triethanolamine (TEA), on the skin wound-healing process was investigated in female Wistar rats. FTIR spectroscopy confirms the presence of carboxylic acid and methyl ester carboxylate groups related with important compounds that confer the hydrogel a good interaction with proteins and growth factors. SEM images show a microstructure and micro-roughness that promote a good adhesion to the wound. Therefore, the swelling kinetics and the contact angle response contribute to the understanding of the in vivo results of the animal test. The results indicated that the Aloe vera hydrogel, prepared with propanediol and TEA, together with its superficial characteristics, improve its rapid penetration without drying out the treated tissue. This produced a positive influence on inflammation, angiogenesis, and wound contraction, reducing 29% the total healing time, reaching the total closure of the wound in 15 days.
... Parabens comprise a group of p-hydroxybenzoic acid esters with alkyl substituents of different lengths, such as methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), and butyl paraben (BuP) (Aubert et al., 2012). They have been widely used as antimicrobial and antifungal agents in personal care products and pharmaceuticals since the mid-1920s (Elder, 1984). The unrestricted use of parabens is under discussion since the beginning of this millennium, when endocrine disrupting properties of different parabens had been observed in in vitro and in vivo studies (Giulivo et al., 2016;Nowak et al., 2018;Oishi, 2001Oishi, , 2002. ...
Background
Parabens are used as antimicrobial preservatives in personal care products. Few studies have dealt with adverse health outcomes, transplacental transfer, and obesogenic effects of prenatal exposure to parabens. We examined the association between placental paraben levels and cord blood metabolic biomarkers, considering modulating effects of maternal pre-pregnancy BMI and underlying epigenetic mechanisms, and investigated longitudinal effects of in utero paraben exposure on early childhood trajectories of BMI z-scores.
Methods
Placental concentrations of four parabens [methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)] were measured by ultra-performance liquid chromatography/tandem mass spectrometry in 229 placentas of the ENVIRONAGE birth cohort. The association with cord blood metabolic biomarkers [glucose, insulin, γ-glutamyltransferase (GGT), high-density and low-density lipoprotein (HDL and LDL)] was analyzed in multiple regression models with two different sets of, a priori selected potential confounders, additionally stratified for different maternal BMI groups and assessed by causal mediation analysis. The association between placental paraben concentration and differential DNA methylation of CpGs annotated to GGT and longitudinal measurements of BMI z-scores were investigated with adjusted linear mixed models.
Results
The geometric means of placental MeP, EtP, PrP, and BuP levels above the limit of detection (LOD) were 4.42, 1.32, 1.51, and 0.35 ng/g respectively, with only EtP showing sufficient (88%) measurements above LOD for further analyses. An interquartile ratio (IQR) increase in placental EtP was associated with an increase of 12.61 % (95% CI: 1.80 24.57) in the geometric mean of cord GGT activity, and with a decrease of −3.64 % (95% CI: −6.80 to −0.39) in the geometric mean of cord glucose. Placental EtP levels were significantly associated with hypermethylation of cg08612779 annotated to GGT7 after correcting for multiple testing (ß = 0.0017, p = 0.049). An interquartile ratio (IQR) increment in placental EtP was associated with a decrease in longitudinal BMI z-score of 0.27 points (95% CI: −0.46 to −0.088).
Conclusion
Prenatal EtP exposure may affect early childhood BMI. The association of placental EtP with cord blood GGT and glucose levels provides a starting point for further research on mechanisms of paraben-related metabolic processes in utero.
... Among them, pharmaceuticals and personal care products (PPCPs) are widespread, persistent pollutants from anthropogenic sources (Soon and Hameed, 2011;Kanakaraju et al., 2018). Parabens are a class of compounds primarily used as antimicrobial preservatives in pharmaceutical products in the mid-1920s (Elder, 1984). However, the use of parabens has extended as preservatives, antimicrobial agents, antifungal agents in cosmetics, and foodstuff (Matwiejczuk et al., 2020). ...
Parabens are a class of compounds primarily used as antimicrobial preservatives in pharmaceutical products, cosmetics, and foodstuff. Their widely used field leads to increasing concentrations detected in various environmental matrices like water, soil, and sludges, even detected in human tissue, blood, and milk. Treatment techniques, including chemical advanced oxidation, biological degradation, and physical adsorption processes, have been widely used to complete mineralization or to degrade parabens into less complicated byproducts. All kinds of processes were reviewed to give a completed picture of parabens removal. In light of these treatment techniques, advanced photocatalysis, which is emerging rapidly and widely as an economical, efficient, and environmentally-friendly technique, has received considerable attention. TiO2-based and non-TiO2-based photocatalysts play an essential role in parabens degradation. The effect of experimental parameters, such as the concentration of targeted parabens, concentration of photocatalyst, reaction time, and initial solution pH, even the presence of radical scavengers, are surveyed and compared from the literature. Some representative parabens such as methylparaben, propylparaben, and benzylparaben have been successfully studied the reaction pathways and their intermediates in their degradation process. As reported in the literature, the degradation of parabens involves the production of highly reactive species, mainly hydroxyl radicals. These reactive radicals would attack the paraben preservatives, break, and finally mineralize them into simpler inorganic and nontoxic molecules. Concluding perspectives on the challenges and opportunities for photocatalysis toward parabens remediation are also intensively highlighted.
... Parabens are p-hydroxybenzoic acid (pHBA) esters with alkyl substituents belonging to methyl, butyl, or benzyl groups (Jonkers et al. 2010). They were first introduced as antimicrobial preservatives in drug products in the mid-1920s (Liebert 1984), while currently serving the same purpose in cosmetics, toiletries, pharmaceuticals, and foods (Daughton and Ternes 1999). By 1987, over 7000 kg/year of parabens were used as additives in cosmetics and toiletries alone (Soni et al. 2005). ...
The impacts of chlorination on methylparaben (MP) removal, as well as of bromide and ammonia on the MP elimination kinetics, were studied. Bromide and ammonia react with chlorine and are promptly transformed into bromine and chloramines, respectively. Rate constants of chlorine, bromine, and monochloramine with MP were determined under different pH conditions. At pH 8.5, the apparent second-order rate constants of MP reactions with chlorine and bromine were found to be 3.37(±0.50) × 10¹ and 2.37 (±0.11) × 10⁶ M⁻¹.s⁻¹ for kChlorine/MP and kBromine/MP, respectively, yet there was low reactivity with monochloramine (kNH2Cl/MP\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\mathrm{k}}_{{\mathrm{NH}}_2\mathrm{Cl}/\mathrm{MP}} $$\end{document} = 0.045 M⁻¹.s⁻¹). Regarding chlorination and bromination, in order to gain further insight into the observed pH-dependence of the reaction, the elementary reactions were considered and the corresponding second-order rate constants were calculated. The experimental and modeled values were quite consistent under these conditions. Then, chlorination experiments with different bromide and/or ammonia concentrations were performed to assess the impact of inorganic water content on MP elimination and a kinetic model was designed to assess MP degradation. Under these conditions, MP degradation was found to be enhanced in the presence of bromide whereas it was inhibited in the presence of ammonia, and the overall impact was pH dependent.
... The 4-hydroxybenzoic acid esters, collectively known as parabens, are a type of antimicrobial preservative used commonly in pharmaceutical formulations. Their antimicrobial action stems from an inhibitory effect on membrane transport and mitochondrial function within microorganisms whereby the antimicrobial effect increases as the chain length of the parabens ester group increases (Elder, 1984). ...
In the present research, the ability of cyclodextrins (CDs) to solubilise and taste mask poorly soluble bitter drugs was assessed by various analytical techniques, including a novel in vitro taste analyser, to propose CDs as excipients for oral liquid paediatric formulations. Corticosteroids were selected as model drugs because of their relevance in paediatrics, whilst model bitter drug quinine was also selected to provide comparative data. Aside from various inclusion complex characteristics, such as stability constants and complexation efficiencies, phase solubility studies determined that: the CDs formed soluble 1:1 inclusion complexes with the corticosteroids studied, the CD derivatives were capable of providing adequate paediatric dose volumes, simulated media in vivo and pH did not to have a major influence on inclusion complexation. The presence of preservatives, however, reduced CD solubility efficiency, whilst reducing the preservative efficiency. ITC studies determined that inclusion complexation with corticosteroids was a spontaneous process and various interactions involved with complexation were proposed. 1H NMR spectroscopy studies indicated that CDs formed inclusion complexes with the corticosteroids, whereby the drug molecules entered the CD cavities via the wider cavity opening. Human taste panel studies demonstrated that CDs were able to taste mask corticosteroids, often more efficiently than traditional taste masking agents, and with 10 times more drug being incorporated in the formulation. Excess CD was also observed to be more efficient at taste masking corticosteroids than molar equivalent concentrations. From these taste panel results, a mechanism of CD taste masking was proposed. Preliminary electronic tongue analysis was found to be able to select concentrations of various taste masking agents for subsequent taste masking assessment. Nevertheless, little correlation was found between the assessment of the electronic tongue and the human taste panel, thus limiting the legitimacy of the instrument for this application. This research has shown that CDs could be utilised in oral liquid paediatric formulations to provide dose uniformity, appropriate volume, and acceptable palatability for poorly soluble bitter drugs. Further work is required to examine the acceptability & bioavailability of these formulations in paediatric patients.
... Given that these compounds are thought to have a low toxicity profile and to be stable in relation to pH and temperature, they are considered safe and, therefore, are widely used in both the food and cosmetic industry to preserve fats, proteins and oils. For this reason, they are regarded as an essential constituent in cosmetics, toiletries and pharmaceuticals (Golden et al. 2005), where they can be used in concentrations of up to 1% (Elder 1984b). According to a survey carried out by Rastogi and colleagues (1995), parabens are a common ingredient in 99% of leave-on and in 77 % of rinse-off cosmetics products. ...
Molecular mechanisms underlying estrogen-induced micronucleus formation in breast cancer cells Aneuploidy, or numerical changes of chromosomes, has been documented in almost all solid tumours and the frequency of micronucleus formation is commonly taken as a biomarker of aneuploidy. An increasing number of observations suggest that exposure to physiologically relevant concentrations of steroidal estrogens gives rise to chromosomal impairments in estrogen receptor competent cells. Although the action of estrogenic compounds is well explained by their ability to bind and activate the estrogen receptor, there are still many uncertainties surrounding the mechanism underlying the ability of steroidal compounds to stimulate micronuclei formation. This has prompted us to investigate whether these effects are linked to activation of the estrogen receptor alpha. Co-administration of tamoxifen and the pure estrogen receptor antagonist ICI 182,780 to breast cancer MCF-7 cells with estrogenic agents did not lead to significant reductions in micronucleus frequencies. Since these anti-estrogens interfere with the transcriptional activity of the estrogen receptor and block promotion of estrogen receptor-dependent gene expression, it appears that this process is not involved in micronucleus formation. In addition to the classical activation of the estrogen receptor at the nuclear level, it is now accepted that estrogenic compounds can rapidly and transiently trigger a number of second-messenger signaling pathways, such as the MAPK cascade Erkl/2 and even their upstream effectors, such as the kinase Src and Raf. Therefore, we wanted to evaluate if the alternative mechanisms of estrogen receptor activation could be involved in the formation of micronuclei by estrogenic compounds. When MCF-7 cells were exposed to estrogenic agents in combination with the specific kinase inhibitors PP2 and PD 98059, reductions in micronucleus frequencies occurred. These findings suggest that the Src/Raf/Erk pathway plays a role in micronucleus formation by estrogenic compounds. Enhanced activation of the Src/Raf/Erk cascade disturbs the localisation of Aurora B kinase to kinetochores, leading to a defective spindle checkpoint with chromosome malsegregation. Further on, using anti-kinetochore CREST antibody staining, a high proportion of micronucleus containing kinetochores was observed when the breast cancer cells were treated with compounds able to activate non-genomic signaling pathways, indicating that such processes are relevant to the induction of micronuclei by estrogens. Our results suggest that estrogens induce micronuclei by causing improper chromosome segregation, possibly by interfering with kinase signaling that controls the spindle checkpoint, or by inducing centrosome amplification. Our findings may have some relevance in explaining the effects of estrogens in the later stages of breast carcinogenesis.
... In a screening of 215 cosmetic products by European and Danish regulatory agencies found that 77 % of these products contained detectable concentrations of parabens ranging from 0.01 % to 0.87 % (w/w), with BP levels reaching a maximum concentration of 0.07 % (w/w) [5]. Parabens have been used as excipients in drug formulations in a wide range of products and delivery routes since 1924 [6]. In the United States, BP is currently approved for use to a maximum concentration of 0.4 % (w/w) in topical creams, 0.08 mg/mL in oral solutions, and 28.4 mg/mL in oral syrups [7]. ...
Butylparaben (BP) is an antimicrobial agent utilized for decades as a preservative in numerous consumer products. The safety of parabens has recently come under scrutiny based on reports of estrogenic activity and suggested adverse effects upon the reproductive system. Due to the limited availability of studies that address the potential for BP exposure to induce reproductive toxicity, and clear evidence of human exposure, the National Toxicology Program conducted a multigenerational continuous breeding study to evaluate the impact of dietary BP-exposure at 0, 5,000, 15,000, or 40,000 ppm on reproductive and developmental parameters in Hsd:Sprague Dawley SD rats. BP-exposure was not associated with adverse alterations of fertility, fecundity, pubertal attainment, or reproductive parameters in F0, F1, or F2 generations. Exposure-dependent increases in liver weights, and incidences of non-neoplastic liver lesions suggest the liver is a target organ of BP toxicity. No findings were observed that would support the purported mechanism of BP-induced endocrine disruption in perinatally-exposed rodents.
... One or more parabens are found in all types of cosmetic products and are used in over 13,200 formulations. 1 They are found in shampoos, commercial moisturizers, shaving gels, personal lubricants, topical/ parenteral pharmaceuticals and spray tanning solution, makeup and toothpaste to stop the growth of fungus, bacteria and other potentially damaging microbes. 2 Parabens are white, odorless, fine crystalline substances that do not discolor cosmetic products and are inexpensive to manufacture. ...
Parabens are widely used in different cosmetic products and their topical application on skin causes systemic absorption of them in the body. Some studies have shown the detrimental effects of parabens on human body including the potential for enhancing the risk of breast cancer. In the past few years, there has been a debate continuing among the researchers, product safety regulators, and cosmetic manufacturers regarding the safety evalution of these widely used preservatives since there are a good number of research works done that signify their breast cancer causing potential and some other harmful effects. Since parabens can potentially lead to many serious health related issues if used in greater amount, the study has been conducted with two aims. One is to determine whether there is presence of parabens in some of the randomly selected international and local cosmetic products and if they contain those, then whether they have the claimed amount of parabens or not. Another aim is to determine the presence of parabens in the consumers who use paraben-containing cosmetic products and also in the control subjects who are not supposed to contain paraben in their blood.
A Shimadzu SIL–20AHT prominence HPLC system controlled by LCsolution LC–Assist Software, version 2.1. with a Shimadzu SPD-M20A prominence Photo Diode Array (PDA) detector (Shimadzu corporation, Kyoto, Japan) was used. Phenomenex® Luna Analytical column (particle size: 5μ, stationary phase: C18 (ODS), pore size: 100 Å) was used under isothermal condition at 40˚C. A binary gradient mode was developed with the water-acetonitrile solvent system with 1.0 ml/min flow rate. The solvent system used was a binary gradient of Water (A) and Acetonitrile (B) at the flow rate of 1.0 ml/min. From the calibration curves of Methyl paraben and Propyl paraben quantitation was done for the parabens in cosmetic samples and blood samples.
In this analysis, the percent quantity was within 0.223 to 4.634 for MP and 0.447 to 2.01 for PP in the 5 cosmetic samples under analysis.
... Parabens are much more susceptible to spore growth cells than vegetative growth of bacteria or fungi. The activity of parabens on low concentration fungi was found [4]. Parabens were considered innocent and hence they have been used as protectives widely, in personal care products for a long time. ...
... MeP, PrP and BPA were the compounds at the highest concentration levels (median concentrations: 822, 256 and 195 ng/g, respectively) and the ones, in addition to PFHpA and PFOS, most frequently detected (frequency of detection from 76 to 100% of the analysed samples) ( Table 1). The distribution pattern of parabens in the analysed hair samples was as follow: MeP (mean 2821 ng/g, median 822 ng/g) N PrP (mean 1006 ng/g, median 256 ng/g) N EtP (mean 635 ng/g, median 47.2 ng/g), which is consistent with the wide usage and long-term accumulation of these compounds and with the fact that MeP and PrP are the most commonly used parabens in cosmetics and food processing (Jiménez-Díaz et al., 2011;Elder, 1984). There was also observed correlation between MeP (neperian logarithm (Ln) MeP) and PrP (Ln PrP) concentrations (r 2 = 0.54; p b 0.05) (Fig. 1). ...
Population is continuously exposed to endocrine disrupting compounds present in everyday products such as parabens, bisphenol A (BPA), and perfluoroalkyl compounds (PFCs). The aims of this study were, first, to evaluate human exposure to three parabens (methylparaben (MeP), ethylparaben (EtP) and propylparaben (PrP)), BPA and six PFCs (perfluorobutanoic acid, perfluoropentanoic acid, perfluorohexanoic acid, perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS)) through the analysis of hair samples from children, women and men and, then, to evaluate possible relationships between pollutant concentration in hair and age, gender, smoking and dyeing habits or hair colour. Hair samples were collected from 42 volunteers from Seville (Spain) (10 children, 16 women and 16 men). Six of the monitored pollutants (MeP, EtP, PrP, BPA, PFHpA and PFOS) were detected in at least 76% of the samples analysed. The highest concentrations and frequency of detection (100% of the samples) corresponded to MeP and PrP (up to 14,187 and 9009 ng/g, respectively). BPA was found in 83% of the samples at concentrations in the range from 24 to 1427 ng/g whereas PFCs were detected at concentrations in the range from 0.6 to 15.5 ng/g, being PFHpA and PFOS the ones most frequently detected (86% and 76%, respectively). Concentrations of BPA and parabens in adults were statistically higher than those in children. The results of this study reveal the suitability of hair for biomonitoring endocrine disrupting compounds of high concern (PFCs, parabens and BPA) to which population is internally or/and externally but continuously exposed.
... Os Parabenos são ésteres do ácido p-hidroxibenzoico que possuem características como boa solubilidade em água, amplo espectro de atividade, além de serem incolores, inodoros e insípidos (AULTON, 2003;SONI et al., 2005). Os parabenos possuem variadas características que tem se tornado evidente quanto ao uso em conjunto, tem maior atividade em faixa de pH 4,5-7,5, quando colocados em água possuem elevada estabilidade, tem largo espectro de atividade antimicrobiana e são eficazes contra bactérias e fungos (ELDER, 1984;SONI et al., 2005). ...
... Parabens are p-hydroxybenzoic acid esters, widely used as antibacterial (Davidson and Branden, 1981;Darbre and Harvey, 2008) and antifungal (Ito et al., 2015) preservatives in packaged food (Liao et al., 2013), cosmetics (El Hussein et al., 2007) and pharmaceuticals (Soni et al., 2005). Shorter the alkyl side chain length of parabens, higher the ability of the compound to penetrate the skin (Elder, 1984;Hatami et al., 2017). Among parabens, methylparaben showed higher permeation, followed by ethylparaben and propylparaben, while butylparaben exhibited lower permeation through the skin. ...
Parabens are widely used as antimicrobial preservatives. Recent studies have reported the endocrine disrupting effects of these chemicals, especially methylparaben. Previously, we have reported the alteration in Vtg gene expression upon exposure to environmentally relevant doses of methylparaben in zebrafish (Danio rerio) embryos. However, studies reporting neurobehavioural outcomes on exposure to methylparaben are limited. Therefore, this study was aimed at investigating the methylparaben-induced effects on developmental and neurobehavioural endpoints. Zebrafish embryos were exposed to sub-lethal concentrations of methylparaben: 0.1 ppb, 1 ppb, 10 ppb and 100 ppb. Alterations in developmental landmarks such as heart rate and hatching percentage were observed in embryos exposed to 10 ppb and 100 ppb of methylparaben. Results obtained from the novel tank diving test established that anxiety-like behaviour is induced in larvae exposed to 0.1 ppb and 1 ppb of methylparaben. A significant inhibition in the acetylcholinesterase (AChE) activity was also recorded in methylparaben-exposed groups. An increase in cortisol levels was observed in the exposed groups, which further supports the observations made in the novel tank diving test, establishing methylparaben as an anxiogenic agent even at sub-lethal concentrations. The underlying molecular mechanism needs further elucidation to investigate whether the behavioural effects are proximally or distally induced by early developmental exposure to methylparaben.
... Seventy years of use have confirmed the excellent safety of Parabens as stable, effective, and nonirritant preservatives. (27,56,57) In 1940, Bonnevie in Denmark described the first case of allergic contact dermatitis from Parabens. (58,59) Allergic dermatitis, eczema is, therefore, often difficult to diagnose, presenting as recalcitrant dermatitis that fails to improve or worsens under seemingly adequate treatment (60,61). ...
Many peoples are exposed daily to cosmetics, pharmaceutical and packaged food products. These products contain Para-hydroxybenzoic acid esters (Parabens). Parabens are synthetically produced preservatives used in personal care products, food and drink, medicines and pharmaceutical preparations. Parabens are readily absorbed through the skin and the gut and excreted in urine. However, some of these compounds may be retained in the body. Parabens have been measured in blood and urine including that of pregnant women, amniotic fluid, placental tissue, cord blood and breast tissue. Parabens are also widespread in our environment. There are many forthcoming types of research evidences that Parabens and Para-hydroxybenzoic acid may act as estrogenic endocrine disruptors. Parabens may increase breast cancer risk, particularly if exposure occurs during critical periods of development. Parabens have been implicated in the proliferation of breast cancer and marine toxicity. This review has been focused on the vital role and research findings of the published literature regarding the deleterious effects of the Parabens.
... Esters of p-hydroxybenzoic acid, known as parabens, are commonly utilized as chemical preservatives. Since the first use reported in 1924 as drug excipients, this chemical class has been experienced a diversification of chemical derivatives and industrial applications (Liebert, 1984). Parabens are currently present in cosmetics, food commodities, pharmaceuticals and industrial products. ...
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Chemosphere
Volume 208, October 2018, Pages 325-334
Photolysis of parabens using medium-pressure mercury lamps: Toxicity effects in MCF7, Balb/c 3T3 cells and Ceriodaphnia dubia
Author links open overlay panelFrancisco E.R.GomesaGermanoTremiliosi-Filhob
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https://doi.org/10.1016/j.chemosphere
Degradation studies of the propylparaben (PrP), butylparaben (BuP) and of the propylparaben-butylparaben mixture (PrP-BuP) in deionized water and surface river water was investigated as a function of pH and initial concentration of the reactants using a medium-pressure mercury lamp. The photolysis of parabens (concentration ranging from 5 to 30 mg L−1) followed apparent pseudo-first-order kinetics, with rate constants (k) in deionized water and surface river water changed from 1.80 × 10−1 to 3.68 × 10−2 min−1 and 1.43 × 10−1 to 1.45 × 10−2 min−1, respectively. Degradation reaction was faster at pH 5 in comparison with pH 7 or 11. The photolysis of parabens was greater than 91%, with low mineralization (26.15%) observed in acidic medium after 95 min. Analysis by chromatography coupled to mass spectrometry (LC-MS/MS) showed that only one product was generated during the degradation reaction and has UV bands similar to 3,4-dihydroxybenzoic acid. Estrogenic activity tests showed that non-degraded parabens stimulated the growth of breast adenocarcinoma (MCF-7) cells and this effect was evaluated after the photolysis. Cytotoxicity assays using fibroblasts cells (Balb/C 3T3 clone A31) indicated that the parental compounds and degradation products were not cytotoxic. On the contrary, non-degraded parabens were toxic to Ceriodaphnia dubia, but the product of photolysis was not. Overall, the photolytic method presented was able to degrade these parabens providing safe and non-estrogenic reaction product.
... Parabens are esters of p-hydroxybenzoic acid that are used as preservatives in a variety of commercial products, including pharmaceutical drugs (Elder, 1984). Paraben exposure is widespread among the U.S. population and is assessed within the National Health and Nutrition Examination Survey (NHANES). ...
Introduction:
Use of paraben-containing medications has been shown to be associated with urinary paraben concentrations among couples undergoing fertility treatment, but it is unknown whether this association is also present among the general population.
Methods:
A list of prescription medications of interest was developed based on their likelihood of containing parabens and the ability to identify users in the National Health and Nutrition Examination Survey (NHANES); alendronate, escitalopram oxalate, fluoxetine, and olanzapine were chosen. Participants reported whether they had used each medication in the past month. Linear regression models were used to compare model-based mean urinary concentrations of each paraben among users and non-users of these four medications.
Results:
A total of 10,302 respondents were included in the analysis, 265 (2.6%) of whom had reported using a paraben-containing prescription medication in the previous month. Users of alendronate had mean concentrations of ethyl paraben that were approximately three-fold higher than non-users (p ≥ 0.001 in unadjusted and adjusted models), which was likely due to three participants with very high concentrations. No other differences in paraben concentrations were found for any of the medications of interest (all p ≥ 0.13). Compared to non-users, a significantly greater proportion of alendronate users had butyl and ethyl paraben concentrations above the 95th percentile (17.8% and 12.3%, respectively) compared to non-users (5.0% and 5.0%, respectively; both p ≤ 0.01), despite ethyl paraben not being an expected ingredient in the brand name formulation of alendronate.
Conclusion:
Despite previous work showing that medications can be an important source of paraben exposure, there was no clear overall evidence of associations between the use of paraben-containing medications and increases in urinary paraben concentrations among participants in NHANES 2005-2012. These results highlight the difficulties inherent in proper assessment of exposures with short half-lives based on a single cross-sectional biologic sample.
Butylparaben (BuP) is regarded as a widespread pollutant, which has potential risk to aquatic organisms. Turtle species are an important part of aquatic ecosystems, however, the effect of BuP on aquatic turtles is not known. In this study, we evaluated the effect of BuP on intestinal homeostasis of Chinese striped-necked turtle (Mauremys sinensis). We exposed turtles to concentrations of BuP (0, 5, 50, and 500 μg/L) for 20 weeks, then investigated the composition of gut microbiota, the structure of intestine, and the inflammatory and immune status. We found BuP exposure significantly changed the composition of gut microbiota. Specially, the unique genus in three concentrations of BuP-treated groups mainly was Edwardsiella, which was not present in control group (0 μg/L of BuP). In addition, the height of intestinal villus was shortened, and the thickness of muscularis was thinned in BuP-exposed groups. Particularly, the number of goblet cells obviously decreased, the transcription of mucin2 and zonulae occluden-1 (ZO-1) significantly downregulated in BuP-exposed turtles. Meanwhile, neutrophils and natural killer cells in lamina propria of intestinal mucosa increased in BuP-treated groups, especially in high concentration of BuP (500 μg/L). Moreover, the mRNA expression of pro-inflammatory cytokines, especially IL-1β showed a significant upregulation with BuP concentrations. Correlation analysis indicated the abundance of Edwardsiella was positively correlated with IL-1β and IFN-γ expression, whereas its abundance was negatively correlative with the number of goblet cells. Taken together, the present study demonstrated BuP exposure disordered intestinal homeostasis through inducing dysbiosis of gut microbiota, causing inflammatory response and impairing gut physical barrier in turtles, which emphasized the hazard of BuP to health of aquatic organism.
Seven selected parabens (4 allowed, 3 banned in cosmetics) were tested in order to confirm and expand historical data on their toxicological properties and safety. The aim was to apply novel in vitro methods, which have been sufficiently technically and scientifically validated for the purposes of toxicological testing of chemicals. The study included several toxicological endpoints such as skin/eye irritation, skin sensitization, endocrine disruption and genotoxicity. The battery of selected methods comprised regulatory accepted EpiDerm™ skin model (OECD TG 439); EpiOcular™ corneal model (OECD TG 492) and scientifically valid test method HET-CAM (DB-ALM Protocol No. 47); in chemico test DPRA (OECD TG 442C); in vitro test LuSens (OECD TG 442D) and in vitro test h-CLAT (OECD TG 442E); Ames MPF™ (Xenometrix) and XenoScreen YES/YAS (Xenometrix). Overall, none of the 4 allowed parabens exhibited skin/eye irritation or genotoxicity. However, all allowed parabens in cosmetics were predicted as samples with potentially sensitizing properties in the LuSens and h-CLAT test methods, but not confirmed by DPRA. Endocrine disruption was recorded only at high concentrations, whereas methyl paraben and ethyl paraben exhibited the lowest activity. This study confirmed the safety of use of the allowed parabens in the highest recommended concentrations in cosmetics or pharmaceuticals.
A novel deep eutectic solvent (DES) with tributyl phosphate (TBP) as hydrogen bond acceptor and d,l-menthol (M) as hydrogen bond donor (HBD) was synthesized for the first time. M, a natural perfume, was selected as the HBD of the promising DES to tailor the extraction capacity and greenify the extraction solvent. The designed TBP-M (molar ratio 1 : 2)-based DES was applied in the simultaneous liquid-liquid microextraction (LLME) of a group of parabens (PBs) and their metabolite (p-hydroxybenzoic acid, PHBA) with wide polarity range in surface water samples. The developed LLME was combined with high-performance liquid chromatography and showed low detection limits (0.5-0.9 μg L⁻¹) and good linearity (R² ≥ 0.9983), precisions (RSDs ≤ 7.6%) and recoveries (86.0% to 110%) under the optimum conditions. The presented procedure has the features of simplicity, inexpensiveness, effectiveness and reliability, and the novel DES has great potential in the highly effective and simultaneous extraction for compounds with different polarities such as PBs and PHBA in complex real water samples.
SCCS OPINION ON Propylparaben - SCCS/1623/20 - Final Opinion
U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, A. Simonnard, W. Uter, N. von Goetz
The SCCS adopted this document at its plenary meeting on 30-31 March 2021 (58 pages)
Published: 17 August 2022
Ed. Publications Office of the European Union, Luxembourg, Luxembourg (58 pages)
ISSN : 1831-4767
ISBN : 978-92-76-54756-3
DOI : https://data.europa.eu/doi/10.2875/607198
Catalog Number : EW-AQ-22-006-EN-N
https://op.europa.eu/fr/publication-detail/-/publication/4c6effa0-21c5-11ed-8fa0-01aa75ed71a1
https://op.europa.eu/fr/publication-detail/-/publication/4c6effa0-21c5-11ed-8fa0-01aa75ed71a1/language-en/format-PDF/source-264497172
The SCCS adopted this document at its plenary meeting on 30-31 March 2021 (58 pages)
Mise en ligne le 15 Avril 2021
https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_243.pdf
Parabens are widely used preservatives in cosmetics and pharmaceutical products and are approved as food additives. These chemicals have been considered safe for many years. However, the literature classifies parabens as endocrine-disrupting chemicals, and an assessment of their influence on the endocrine system and systemic toxicity is important. This study explored long-term systemic toxicity, effects on the endocrine system, and toxicokinetic behavior after repeated subcutaneous administration of butylparaben to Sprague–Dawley rats. Rats were treated with vehicle (4% Tween 80) or butylparaben at dose levels of 2, 10, and 50 mg/kg/day for 13 weeks. Assessment of systemic toxicity and endocrine-disrupting effects was based on mortality; clinical signs; body weight; food and water consumption; ophthalmological findings; urinalysis; hematology and clinical biochemistry; organ weights; necropsy and histopathological findings; regularity and length of the estrous cycle; semen quality; and toxicokinetic behavior. Female uterine weight and estrous cycle, and male semen quality indicated no estrogenic effects. Butylparaben induced local irritation at the injection site in both sexes at a dose of 50 mg/kg/day, but systemic toxicity was not observed. Therefore, the no-observed-adverse-effect level of butylparaben is set at 50 mg/kg/day in rats of both sexes. Butylparaben was without endocrine system effects at this dose. Butylparaben displays dose-dependent systemic exposure up to the maximum dose of 50 mg/kg/day and repeated administration of butylparaben for 13 weeks shows no bioaccumulation.
Parabens have been widely employed as preservatives since the 1920s for extending the shelf life of foodstuffs, medicines, and daily care products. Given the fact that there are some legitimate concerns related to their potential multiple endocrine-disrupting properties, the development of novel bioanalytical methods for their biomonitoring is crucial. In this study, a fabric phase sorptive extraction reversed-phase liquid chromatography method coupled with UV detection (FPSE-HPLC-UV) was developed and validated for the quantitation of seven parabens in human plasma samples. Chromatographic separation of the seven parabens and p-hydroxybenzoic acid was achieved on a semi-micro Spherisorb ODS1 analytical column under isocratic elution using a mobile phase containing 0.1% (v/v) formic acid and 66% 49 mM ammonium formate aqueous solution in acetonitrile at flow rate 0.25 mL min−1 with a 24-min run time for each sample. The method was linear at a concentration range of 20 to 500 ng mL−1 for the seven parabens under study in human plasma samples. The efficiency of the method was proven with the analysis of 20 human plasma samples collected from women subjected to breast cancer surgery and to reconstructive and aesthetic breast surgery. The highest quantitation rates in human plasma samples from cancerous cases were found for methylparaben and isobutylparaben with average plasma concentrations at 77 and 112.5 ng mL−1. The high concentration levels detected agree with previous findings for some of the parabens and emphasize the need for further epidemiological research on the possible health effects of the use of these compounds.
Layered double hydroxide (LDH) as nano‐carrier of parahydroxybenzoate (listed in EC Directive 10/2011) was coated on a biodegradable film of cellulose acetate, coupled with compostable cellulose cardboard and trays realized. The sustained release of parahydroxybenzoate ionically intercalated into the LDH resulted significantly slower than the parahydroxybenzoate free dispersed into the coating medium. Such active packaging showed significant antimicrobial activity against Salmonella enterica Typhimurium, Escherichia coli, Listeria monocytogenes and Lactobacillus sakei. It was more than one in all cases, ranging from 1.1 for E. coli to 2.6 for S. enterica Typhimurium. Overall migration tests in ethanol at 50% (v/v), as food simulant, showed that the prepared packaging is suitable for food contact, being the migrated amount below the limits imposed by the EU regulation. Fresh‐cut iceberg lettuce was packed into the prepared active packaging and in a control packaging with no active coating and stored in condition of thermal stress (i.e. 10°C). Organoleptic characteristics and the evolution up to 14 days of mesophilic lactic bacteria, total bacteria count, yeasts and moulds showed a significant inhibition of such strains from the active filler. Comparing the lettuce packed in control and active packaging, for mesophilic lactic bacteria, it was found a delta log of 0.24 (CFU), and for the total bacteria count, a delta log of 1.63 (CFU). The most significant effects were observed respect to yeasts and moulds and yeasts counts. For yeasts, it was observed a delta log of 2.32 (CFU), and for yeasts and moulds, a delta log of 2.5 (CFU). The prediction of the shelf life of the lettuce was done following the growth of E. coli up to 30 days through the Gompertz equation. It was found a prolongation of the shelf life from 11 to 16 days
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.
SCCS OPINION ON Propylparaben - SCCS/1623/20 - Preliminary Opinion
U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, J. Ezendam, E. Gaffet, C. L. Galli, B. Granum, E. Panteri, V. Rogiers, Ch. Rousselle, M. Stepnik, T. Vanhaecke, S. Wijnhoven, A. Koutsodimou, A. Simonnard, W. Uter, N. von Goetz
The SCCS adopted this document at its plenary meeting on 27-28 October 2020 (57 pages)
Mise en ligne le 6 Novembre 2020
https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_243.pdf
Methylparaben (MeP) is widely used as preservative in personal care products, food commodities and pharmaceuticals due to its antimicrobial properties. Its widespread use resulted in the contamination of aquatic environment and raised concerns about the potential adverse effects on human health, especially in the developing organisms. The aim of the present study was to evaluate the embryotoxicity of MeP in zebrafish early-life stages applying the benchmark-dose (BMD) methodology to Fish embryo acute toxicity (FET) tests-OECD guideline 236. Toxic effects were studied by daily evaluation of lethal endpoints, hatching rate and sublethal alterations. Zebrafish fertilized eggs were exposed until 96 h post fertilization (hpf) to five concentrations of MeP: 1 mg/L, 10 mg/L, 30 mg/L, 60 mg/L and 80 mg/L. The lethal concentration 50 (LC 50) was 72.67 mg/L. Indeed, BMD confidence interval (lower bound, BMDL-upper bound, BMDU) was 40.8–57.4 mg/L for lethal endpoints and 16–26.5 mg/L for toxicity index, that includes both lethal and sublethal alterations. Zebrafish embryos exposed to MeP developed sublethal alterations including pericardial edema, yolk edema, blood stasis, reduction in blood circulation, reduced heartbeat and notochord curvature. The number of embryos exposed to the highest concentrations of MeP that reported sublethal alterations increased between 24hpf and 48 hpf-72 hpf-96 hpf. Only zebrafish larvae treated with 30 mg/L of MeP showed behavioural changes. This study highlighted the detrimental effects of MeP on zebrafish early-life stages with attention to its developmental toxicity.
Cosmetics are a source of lifetime exposure to various substances including parabens, being the most popular synthetic preservatives. Because the use of cosmetics shows an increasing trend and some adverse health outcomes of parabens present in these products have been reported, the present review focused on the safety of dermal application of these compounds. Special attention has been paid to the absorption of parabens and their retention in the human body in the intact form, as well as to their toxicological characteristics. Particular emphasis has been placed on the estrogenic potential of parabens. Based on the available published data of the concentrations of parabens in various kinds of cosmetics, the average ranges of systemic exposure dose (SED) for methylparaben, ethylparaben, propylparaben, and butylparaben have been calculated. Safety evaluations [margin of safety (MoS)] for these compounds, based on their aggregate exposure, have also been performed. Moreover, evidence for the negative impact of methylparaben on skin cells has been provided, and the main factors that may intensify dermal absorption of parabens and their impact on the skin have been described. Summarizing, the use of single cosmetics containing parabens should not pose a hazard for human health; however, using excessive quantities of cosmetic preparations containing these compounds may lead to the development of unfavorable health outcomes. Due to the real risk of estrogenic effects, as a result of exposure to parabens in cosmetics, simultaneous use of many cosmetic products containing these preservatives should be avoided.
Parabens have been widely used as antimicrobial preservatives in cosmetics, pharmaceuticals, foods, and beverages. Commonly, methyl‐, ethyl‐, propyl‐, and butylparaben are used independently or in combination to maintain the quality of industrial products, and they are considered to have low toxicity. However, recent evidence has suggested that parabens are toxic in mammalian cells, and parabens have been associated with allergic‐contact dermatitis, breast cancer, and changes in testosterone levels. Sulforaphane, a cruciferous vegetable‐derived isothiocyanate, was effective in decreasing the growth inhibitory concentrations of ethyl‐, propyl‐, butyl‐, and methylparaben in the yeast Saccharomyces cerevisiae. The sulforaphane‐enhanced fungicidal effects of methylparaben were deemed to be caused by drastic cell membrane damage and the leakage of internal substances, such as nucleotides, from S. cerevisiae cells. Moreover, sulforaphane markedly decreased the minimum concentration of methyl‐ and ethylparaben required to inhibit the growth of various microbes, such as the pathogenic yeast that causes severe mycosis, Candida albicans; the filamentous fungi Aspergillus niger; and the gram‐negative bacterium Escherichia coli. Enhanced antimicrobial activity from the beneficial components of edible plants may increase paraben efficacy at low concentrations and minimize preservative‐induced side effects in consumers.
The solubility of methylparaben was determined in acetonitrile + water mixtures at several temperatures (278.15 K to 318.15 K). The solubility curves as a function of acetonitrile ratio showed a maximum at a mass fraction of acetonitrile 0.85 at all temperatures. In all cases, the homogeneous mixture splits into two liquid immiscible phases. The concentration range at which phase separation takes place is 0.35–0.70 in a mass fraction of acetonitrile, showing a clearer separation at higher study temperatures. According to the results of DSC, this phase separation was not related to solid phase changes (polymorphism). The apparent enthalpy of the solution process was a nonlinear function of the acetonitrile ratio, and the solution process of the drug is endothermic and enthalpy determined. Finally, the enthalpy-entropy compensation analysis shows a non-linear behaviour, possibly due to the influence of acetonitrile in the solution process of methylparaben in cosolvent acetonitrile + water mixtures.
Paraben derivatives are widely used as an antifungal, antimicrobial preservative in cosmetic products, pharmaceuticals, and food. These molecules are called endocrine disruptors (EDCs). The exposure of the human body to paraben derivatives needs further study and for this purpose 200 urine samples were collected from Tunisian men and women aged between 5 and 90 years to determine three paraben derivatives: methylparaben (MP), ethylparaben (EP) and propylparaben (PP) using ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). The three major parabens were found in 95 urine samples. The obtained results indicate that MP, EP, and PP were detected in 57%, 46%, and 40% of all samples, respectively. Urinary concentration for the three parabens was in the range of 0.88-84.46 ng/mL, 0.52-29.2 ng/mL, and 0.51-28.17 ng/mL of PP, MP, and EP, respectively. In addition, the concentrations of the paraben derivatives in women were higher than those of men. These findings indicate that the exposure occurs from common products (foods, cosmetics, and pharmaceuticals). The Tunisian authorities should control the composition of packaging of these common products in order to protect humans against EDCs.
Parabens have been widely used as preservatives in the cosmetics, food, and pharmaceutical industries for more than 70 years. Monitoring for paraben allergy closely followed with studies reporting paraben testing in standard screening fashion as early as 1940. The frequency of sensitivity to this widely used biocide has remained low and remarkably stable for many decades despite extensive use and progressive expansion of utilization worldwide. The authors select paraben mix as the (non)allergen of the year. Paraben reactions are quite uncommon and generally relevant. Parabens remain one of the least allergenic preservatives available. The unsubstantiated public perception of paraben safety has led to its replacement in many products with preservatives having far greater allergenic potential. This report reviews the well-established safety of parabens from an allergologic standpoint.
Parabens are used as preservatives in many consumer products and human exposure to these chemicals has been a public concern. In this study, mollusks (n = 186), collected from the Chinese Bohai Sea during 2006-2015, were analyzed for six parabens and their five metabolites. The total concentration of parabens was in the range of 2.66-299 ng/g dw (geometric mean: 24.1). Methyl paraben and 4-hydroxybenzoic acid were the predominant parent and metabolic parabens, respectively found in mollusks. Mollusk species, Mactra veneriformis, Mytilus edulis, and Cyclina sinensis contained elevated concentrations of both parent and metabolic parabens. A gradual increase in paraben concentrations was found in mollusks collected between 2006 and 2012. Principal component analysis suggested the existence of a common source for these chemicals in mollusks. Consumption of mollusks can contribute to human exposures and we estimated daily intakes of parabens through the consumption of mollusks. This is the first study to report temporal trends and accumulation of parabens and their metabolites in a variety of invertebrate species from coastal marine environments.
Inhibition of Salmonella typhimurium and Staphylococcus aureus in Trypticase Soy Broth by the propyl ester of p-hydroxybenzoic acid (propyl paraben, 0 to 500 ppm) and butylated hydroxyanisole (BHA, 0 to 400 ppm) alone and in combination was studied. A concentration of 200 ppm of BHA was bactericidal to S. aureus , while up to 400 ppm of BHA was only restrictive to the growth of S. typhimurium . A gradual decline in viable cell numbers of S. aureus was noted with addition of 500 ppm of propylparaben while an initial reduction of S. typhimurium and subsequent growth occurred at a level of 300 ppm of propylparaben. A combination of 50 ppm of BHA-propylparaben was needed to produce a gradual reduction in viable cells of S. aureus and 150 ppm of each additive caused S. typhimurium to exhibit an apparent decrease in cell numbers and then limited growth.
The ether-type glucuronide of p-hydroxybenzoic acid was isolated from the urine of rabbits receiving methyl p-hydroxybenzoate and its structure was established as p-car-boxyphenyl-β-D-glucopyranosiduronic acid. Three main metabolites, p-hydroxybenzoic acid, p-hydroxyhippuric acid, and the ether-type glucuronide, were identified in the urine, and the ester-type glucuronide and p-carboxyphenyl sulfate were proved as minor metabolites by means of paper chromatography. © 1962, The Pharmaceutical Society of Japan. All rights reserved.
More than two kinds of the preservatives are used frequently, in the market foodstuffs. In this paper, the separating determination method for the preservatives by use of the column of the strongly basic ion-exchange resin (DOWEX 2X8-Cl⁻ form) was described. As the eluents, the hydrochloric acid mixed with methanol of the various concentrations were used selectively. The results obtained from the experiments are as follows: 1) For seven examples of the mixtures of preservatives, the separating methods of their ingredients were accomplished. 2) The interference of the other substances such as the decomposed products from sugar, vanillin and ethyl vanillin, could be romoved from the preservatives. © 1971, Japanese Society for Food Hygiene and Safety. All rights reserved.
Methods for the determination of six preservatives used in solid, semi-solid, and liquid foods were examined. Extraction procedures were divided into four steps : Step 1 : Extraction of preservatives from food with organic solvent. Step 2 : Separation of the preservatives from fatty substances by transfer of the former into an alkaline solution. Step 3 : Acidification of the alkaline layer with an acid followed by re-extraction of the acidic layer with an organic solvent. Step 4 : Concentration of organic solvent in vacuo and injection of an aliquot of the concentrate into an FID gas chromatograph. In Step 1, the homogenization and organic solvent extraction were carried out simultaneously in a Waring blender, since it had been confirmed that removal of protein and fat by use of suitable precipitant did affect the recovery of the preservatives. Ether was found to be suitable for the organic solvent of extraction. In Step 2, it became clear that the normality of the alkaline solution used must not be lower than 0.2. In order to avoid hydrolysis of p-hydroxybenzoates, 0.4 N potassium hydroxide solution in 50% methanol was finally chosen. In Step 3, the final pH of the solution must be brought to lower than 2 so that the preservatives may be successfully re-extracted with ether. In Step 4, the conditions for gas chromatography were as follows : Glass tube, 2 m in length, packed with 5% DEGS+1% H3PO4/Chromosorb W 60-80 mesh, column temp., 144° ; injection temp., 190° for sorbic acid, dehydroacetic acid, benzoic acid and salicylic acid ; glass tube, 1.5 m in length, packed with 3% SE-30/Chromosorb W 60-80 mesh, column temp., 180° ; injection temp. 230°for ethyl p-hydroxybenzoate and buthyl p-hydroxybenzoate. Recoveries were measured on Samsoe cheese, cream cheese, blue cheese, butter, wines, pickles, Korean ginseng extract, and honey, spiked at either 200 or 20 ppm of each preservative excluding SA. The recoveries at 200 ppm level ranged from 86.4 to 99.4%, while at 20 ppm level the recoveries were 84.0-95.1%. The minimum detection level of the 5 preservatives was 2 ppm.
The paper electrophoretic method to separate and identify eight preservatives (salicylic acid, benzoic acid, sorbic acid, dehydroacetic acid, ethyl p-hydroxybenzoate, resorcinol, β-naphthol and p-chlorobenzoic acid), a sterilizer (nitrofurazone), and three artificial sweetners (saccharin sodium, sodium cyclamate and dulcin) was investigated by using 1% borax solution, Kolthoff buffer solution (pH 4.0 and 5.8) or Atkins-Pantin buffer solution (pH 10) as the electrolyte. The mobilities of the compounds were shown as the relative one to flavianic acid, and tabulated. All the compounds could be identified by selecting the electrolytes.
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
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)
Application of programmed temperature gas chromatography (GC) has been reported for fatty acids etc., but has not been used routinely in the determination of food additives.A Shimadzu Model GC-1C gas chromatograph, equipped with a flame ionization detector and temperature-programming apparatus, was used in our investigation. Simultaneous gas chromatographic determination was tried on six synthetic preservatives. However, accurate quantitative determination of sorbic acid, dehydroacetic acid and benzoic acid cannot be expected because the retention times of the peaks of these preservatives were so early that these peaks showing might be masked in the peak of the solvent.Thus simultaneous determination of preservatives both early and late retention times was possible only by use of the programmed temperature GC with FID.It was known that the application of programmed temperature was not always followed with accurate results, because both values of the relative peak area and the relative factors were affected by the different programmed gradients of temperature as compared with the case of isothermal operation.However, the values obtained by programmed temperature operation must not be theoretically different from those determined under isothermal conditions.As the results, the calibration curves, obtained by peak area ratio of each preservative to internal standard, show linearity within a range from 10 to 70μg for SoA and from 2 to 8μg for the others.
Contact sensitivity to parabens incorporated as preservatives in topical steroid creams is reported. The optimum patch test concentration for detecting this sensitivity is 5% paraben in petrolatum. Patch tests to the offending steroid creams or bases with their lower paraben concentrations may give false negative reactions. The possibility of unrecognized paraben sensitivity as the cause of a protracted contact dermatitis should be considered in patients treated with parabencontaining creams, even after other sensitizers such as neomycin sulfate and iodochlorhydroxyquin (Vioform) have been identified and eliminated.
Four thousand consecutive patients with eczema in five European clinics were tested with a series of medicaments. These included 20% neomycin sulfate, 5% benzocaine, 5% iodochlorhydroxyquin (Vioform), 15% parabens, 30% wool alcohols, and 5% chlorquinaldol (Sterosan), in a petrolatum vehicle.
Of the 4,000, 560 (14%) were judged to have a relevant medicament dermatitis; this represented one third of all allergic contact dermatitis in this series. Forty percent of women with dermatitis of the lower leg had medicament sensitivity. Benzocaine and neomycin elicit positive reactions most frequently, wool alcohols somewhat less, whereas iodochlorhydroxyquin, chlorquinaldol, and parabens give less than 2% positive reactions. In spite of the geographical differences, greater than 80% of applied medicament dermatitis could be diagnosed with the standard patch test series.
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
During the course of investigations on the effect of antiseptics for foodstuff on a Lactobacillus casei-phage J 1 system, we have found that alkyl esters (n-butyl, isobutyl, n-propyl, isopropyl and ethyl) of p-hydroxybenzoic acid are new lysing agents for phage-infected cells. Unlike streptomycin, a known lysing agent in this system, the esters induced premature lysis of infected cells when they were added during the whole of the latent period. The infecting phage was lost and no new phage was produced. The lysing activity of the esters increased with an increase in the number of carbon atoms in the alkyl chain: butyl>propyl>ethyl. Free p-hydroxybenzoic acid, not esterified, had no lysing activity. At the available concentrations, the esters inhibited the growth of uninfected cells, but did not cause their lysis. The lytic reaction induced with the esters is not due to phage-endolysin, but may be caused by the increase in the permeability of the cytoplasmic membrane with phage infection. Esters of p-hydroxybenzoic acid could be used not only to determine the intracellular phage (free phage was not inactivated under the conditions of lysis induction), but also to elucidate the intracellular events during the eclipse period. The effect of esters of p-hydroxybenzoic acid on a L. casei-phage J 1 system was also described. © 1973, Japan Society for Bioscience, Biotechnology, and Agrochemistry. All rights reserved.
The biological fates of ethylparaben (EP) which has been widely used as a preservative for the pharmaceutical preparations and foods, and p-hydroxybenzoic acid (HB) which is the parent compound of EP, were investigated at the dose of practical usage (2 mg/kg) in rats. Although both EP and HB were metabolized to glycine conjugate (M1), ester type glucuronide (M3) and sulfate (M4) of HB and excreted in the urine and bile, the excretion ratios were different as compared with the results of higher dose experiments carried out by other authors, and a route dependency was also found in the rate of excretion in the bile. The excretion data obtained in this study are shown as follows: In intravenous administration of EP, the excreted total activity was 91.3% per dose in the urine and 5.97% in the bile, and percentages per dose of the major metabolites excreted in the urine were 8.14% of HB, 39.6% of M1, 29.5% of M3 and 6.48% of M4. In intraduodenal administration of EP, the excreted total activity (83.5%) and the activity excreted as HB (3.51%) decreased compared with the intravenous administration. In the HB administration, the route dependency of the total activity was not found, but a decrease in the excretion of HB in the intraduodenal administration was found. The excretion of total radioactivity almost ceased by 5 hr and the biological half-lives obtained from the β-phase of the sigma-minus plots of the metabolites excreted in the urine were 40-70 min. The results obtained in this study differ from those of other authors at the high dose experiments.
AbstractA simple and rapid polyamide chromatographic method for the detection of 12 kinds of preservatives and 3 kinds of artificial sweeteners were reported. The results indicated that the method was good in sensitivity, separability and reproducibility.
Summary The preservatives sorbic acid, benzoic acid, methyl-, ethyl-, propylester of p-hydroxybenzoic acid and propionic acid can be determined quantitatively in one step by isotachophoretic separation based on the different electrophoretic mobilities of these compounds. The determination involves a direct extraction step in the so called Extrelut-columns, where the preservatives are separated from the food sample, mainly from the lipid phase. The whole analysis procedure is short and recoveries for the preservatives in the samples tested are very good. There is no interference by other substances and the range of concentrations for which a determination is possible is large and encompasses virtually all concentrations used in commercial practices.
Die bei 37,5° mit Sauerstoffgesättigter Tyrodelösung durchströmte Mäuseleber hydrolysierte mindestens 0,151 mg p-Oxybenzoesäureäthylester/g Leber/min zu p-Oxybenzoesäure.
Nach peroraler Aufnahme von 10–20 mg Ester/kg Körpergewicht lassen sich im Serum des Menschen in den folgenden 4 Std kein freier Ester, aber p-Oxybenzoesäure nachweisen.
Nach peroraler Verabreichung von 25, 100 und 500mg Ester/kg ist in den folgenden 8 Std im Serum des Hundes nur nach 500 mg/kg unveränderter Ester nachweisbar. Die p-Oxybenzoesäurekonzentrationen des Serums entsprechen den verabreichten Estermengen.
Nous avons étudié sous quelle forme l'acide p-hydroxybenzoïque et les estersméthylique, éthylique et propylique sont éliminés par le rat et quelle est la vitesse d'apparition de l'acide phénolique et de ses métabolites dans l'urine. Nous avons pu mettre en évidence dans l'urine par chromatographie sur papier et révélation par le réactif de Mi11on de l'acide p-hydroxybenzoïque, de l'acide p-hydroxyhippurique, de glycuronide sous forme d'esters, un éthérosulfate, un dérivé glycuronyle et un composé non identifié. Une étude de la cinétique d'apparition de l'acide phénolique et de ses métabolites dans l'urine nous a montré que, tout d'abord, il apparaissait de l'acide p-hydroxybenzoïque libre, puis appairaissent le glycuronide, l'acide p-hydroxyhippurique dont la concentration croit en même temps que décroit celle de l'acide p-hydroxybenzoïque libre. An cours de l'expérience la concentration dans el sang de l'acidephénolique reste extrêmement faible.
The authors have endeavoured to set up a rapid, and widely applicable technique for the qualitative detection of some antiseptics in foodstuffs. Among the wide range of existent antiseptics a choice has been made of those that are most commonly used. That means benzoic acid, parahydroxybenzoic acid, salicylic acid, sorbic acid, monobromacetic acid, monochloracetic acid and their esters. These preserving agents have been sought for in foodstuff as various as mayonnaise and salad dressing, biscuits, bread, meat, alcoholic and non alcoholic drinks, etc...
Their extraction is carried out mainly, after defecation with Carrez solutions, by means of a mixture of petroleum ether and ether in equal proportions.
After concentrating the extract to a very reduced volume, quantities of about 50 gamma have been applied on the chromatographic plate. At least two chromatograms with two different supports and solvents were carried out, giving for each product different Rf values, ensuring thus a better identification in doubtfull cases.
These technics, coupled if necessary with the use of specific colored reactions, allow to identify with certitude each of the studied antiseptics. The sensitivity of the method with a general developer for the thin layer chromatography can be evaluated to about 30 gamma for benzoic, sorbic, monochlor and monobromacetic acids. For salicyclic acid, this level can be as low as 5 gamma.
Although parahydroxybenzoic acid esters have not been examined separately, they can be easily detected as acids after saponification of the ether extract. This bulk identification of the esters will be probably sufficient insofar as the law in most countries does not authorize the use of any one of them.
Zusammenfassung Zur routinemäßigen Überwachung von Lebensmitteln auf Vorkommen von einem oder mehreren von 11 verschiedenen Konservierungsmitteln sowie von Saccharin wurde eine papierchromatographische Methode angewandt. Die Identifizierung der Substanzen geschieht durch Beobachtung des mit kurzwelligem Ultraviolettlicht (2537 Å) beleuchteten Papiers vor und nach der Behandlung mit verschiedenen Reagentien.
Die Konzentrationen von p-Oxybenzoesäureestern, die in einer Nährbouillon vom pH 5.5 eine völlige Wachstumshemmung der verschiedenen Testmikroorganismen bewirken, werden ermittelt. Die Wirksamkeit der Ester nimmt ganz allgemein mit der Kettenlänge der Substituenten zu. Die Testmikroben erweisen sich als unterschiedlich resistent. Milchsäurebakterien zeigen eine weitgehende Unempfindlichkeit gegen einige p-Oxybenzoesäureester. Der Vf. stellt abschließend die Anwendung von p-Oxybenzoesäurebutylester als Konservierungsmittel in Lebensmitteln zur Diskussion.Antimicrobial Activity of the Esters of p-Hydroxy Benzoic AcidThe concentrations of p-hydroxy benzoic acid esters, which inhibit the growth of various testmicro-organisms in a nutrient broth at a pH of 5.5, have been determined. The antimicrobial activity of the esters increases generally with the increase in the chainlength of the alkyl groups. Different testmicrobes have been found to react differently to the action of the reagents. Lactic bacteria are almost immune to the action of some of the p-hydroxy benzoic acid esters. The author concludes with a discussion on the application of butyl p-hydroxy benzoate as a food-conservative.
Methyl p-hydroxybenzoate was assayed accurately and precisely by UV spectroscopy after separation from its hydrolytic degradation product, p-hydroxybenzoic acid. The complete separation was effected by adsorption chromatography on a column of diatomaceous earth. The method was compared to the USP XVIII GC procedure and to a direct UV spectrophotometric procedure.
The frog, Rana pipiens, was found to take up certain p-hydroxybenzoates when partially immersed in a solution of these substances. The order of decreasing uptake rates for the benzoates was butyl, propyl, ethyl, and methyl. The presence of a nonionic surfactant, polysorbate 20, reversed the order; however, a biological surfactant, sodium cholate, appeared to increase the rate of uptake of the parabens. The process was first order.
Some of the esters of p-hydroxybenzoic acid have been separated and identified by direct gas chromatography. The trimethylsilyl ethers of these compounds lend themselves more readily to gas chromatography since they show little or no tailing and therefore can be measured quantitatively. The method is rapid and sensitive.
Summary Size rather than weight differences are emphasized as the basis for gel permeation chromatographic separations. Examples of
the separations available with a new packing material, μStyragel are given for low molecular weight compounds.
Incorporation of methyl-, ethyl-, and butylparabens into sodium lauryl sulfate (SLS) micelle was examined by measurement of ultraviolet spectra, conductance, degree of counterion binding to the micelle, and elution volume of micelles solubilizing alkylparabens. The results show that alkylparabens penetrated only a little into the palisade layer. This phenomenon was closely related to the diluted charge density of micellar surface and the decrease of micellar volume by the solubilization. The factors for stabilization of the micelle by solubilization of alkylparabens were assumed as reduction of the free energy of a micelle due to the diluted surface charge density on a micelle, the entropy of mixing of the mixed micelle, and the decrease of activity coefficient of SLS molecule in the mixed micelle, γ∗m, which may be considered as geometrical factors. Among these geometrical factors the hydrophobic interaction between alkylparaben and the hydrocarbon part of SLS micelle will be of importance.
In Versuchen mit Testsubstanzen wurden Verfahren zum papierchromatographischen Nachweis von verschiedenen Konservierungsmitteln ausgearbeitet. Hiernach lassen sich Benzoesäure und Dehydracetsäure in Margarine schnell und eindeutig qualitativ nachweisen. Auch wurde in die Lackschicht von Aluminiumfolie eingearbeitete Dehydracetsäure qualitativ nachgewiesen.Paperchromatographic Studies on some PreservativesExperimenting with test-substances, methods for the paperchromatographic establishment of various preservatives were worked out. Accordingly the presence of benzoic acid and dehydroacetic acid in margarine can be established quickly and specifically. Also dehydroacetic acid in the lacquer film of aluminium foil could be determined qualitatively.
Die durch Wasserdampfdestillation aus dem Lebensmittel isolierten Konservierungsmittel werden dünnschichtchromatographisch (1. Mitt.) bzw. durch Farbreaktion (Formaldehyd aus Hexamethylentetramin) nachgewiesen. Zur Bestimmung wurden colorimetrische Verfahren ausgewählt. Sie werden diskutiert und Änderungsvorschläge gegenüber den Originalvorschriften begründet. Lediglich für die Bestimmung der PHB-Ester ist ein gesondertes Extraktionsverfahren erforderlich; alle anderen Arbeitsgänge können in einem Wasserdampfdestillat durchgeführt werden. Die Arbeitsvorschriften werden mitgeteilt. Ein Untersuchungsschema gibt den Analysengang wieder.
Detailed growth curves based on progressive turbidity readings have been used to study the inhibition of Aerobacter aerogenes Type I, by a series of alkyl 4-hydroxybentoates. Results in the lag phase are irregular, but it is apparent that the elongation of this phase becomes very marked at the higher concentrations of the inhibitor and that complete inhibition of growth occurs at a concentration that extends lag indefinitely rather than at one which reduces the growth rate to zero. Inhibition in the logarithmic phase, plotted as a function of inhibitor concentration, gives curves convex to the abscissa that contrast with experience of fungi, where characteristic concave adsorption forms have been obtained. However, the convexity of the present series of curves is likely to be a reflection of secondary effects associated with this method of determining bacterial inhibition, particularly in that there is a loss of viability in cells exposed to the higher concentrations. Determinations based on stationary populations arc convenient and give good agreement between experiments, but are not necessarily related in any simple fashion to growth rate inhibition.
Although the order of increasing activity with increasing chain length of the esters is similar that found for fungi the activity of the methyl ester is less against Aerobacter aerogenes so that solubility difficulties soon prevent the attainment of a reasonable level of inhibition.
Growth curve methods that use a relatively small inoculum with consequent lag phase of variable length do not appear well suited for a direct study of growth rate inhibition.
Growth curve method that use a relatively small inoculum with consequent lag phase of variable length do not appear well suited for a direct study of growth rate inhibition. A simple method better suited to this purpose is being developed.
Metabolic studies conducted on the ethyl and n-propyl esters of 14C-labelled p-hydroxybenzoic acid orally administered to cats at a dose level equivalent to 130 of the parent acid, have shown that from both of these compounds radioactivity is rapidly excreted in the urine within 72 h. Examination of the urine of these animals by thin-layer and DEAE-Sephadex A-25 chromatography revealed two major metabolites, one of which was identified as p-hydroxyhippuric acid, and the other as free p-hydroxybenzoic acid. A parallel study on the metabolism of a single oral dose of 14C-labelled p-hydroxy-enzoic acid of 130 showed that, as with the esters, substantially all of the radioactivity was excreted in the urine within 72 h. However, only one urinary metabolite, p-hydroxyhippuric acid was found in this experiment.
The separation of preserving agents and especially of benzoic acid and sorbic acid by thin-layer chromatography was studied. Both preservatives can be separated on cellulose chromatoplates using the upper phase of the solvent mixture n-butanol—35% ammonia—water (70:20:10). Still better and much more rapid separations are obtained on chromatoplates coated with a kieselgel G—kieselgur G(1:1) adsorbent mixture, especially when developing the plate with the mobile phase hexane—acetic acid (96:4).Several specific colour reactions are described which can be applied in the analysis of the preservatives isolated from food products, packaging material etc.
A case report and review of the literature of paraplegia following intrathecal chemotherapy with methotrexate and cytosine arabinoside is presented. Autopsy identified damage to the spinal nerve roots within the subarachnoid space, which accounted for the neurologic deficit. The only substances common to both chemotherapeutic agents were their preservatives, methylhydroxybenzoate and benzyl alcohol, which were used, in the diluent. Prolonged exposure to these preservatives is known to cause severe neurotoxicity. Though the specific agent responsible for paraplegia following intrathecal chemotherapy is unknown, there is evidence to suggest that the preservatives rather than the therapeutic agents themselves are responsible.
Onze sparations de produits pharmaceutiques rencontrs dans des mdicaments varis ont t effectues par chromatographie en phase liquide rapide sur silice du type sphrosil 5 m: noscapine-promthazine; malate de mpyraminebromhydrate de dextromthorphane; parahydroxybenzoates de mthyle et de propyle; amidopyrine et butazolidine; mthaqualone et paractamol; paraoxypropione, phnobarbital et mthylthiouracile; benzocane-chlorhydrates de procane et de ttracane; phnobarbital, chlorhydrate de papavrine et thophylline; phnobarbital, cafine, amidopyrine et nicotinamide; biclotymol, chlorhydrate de nosynphrine, paractamol et gaacolate de glycryle; lignocane, actate d'hydrocortisone et butazolidine. A l'exclusion de la dernire, toutes ces sparations sont effectues avec un solvant unique; d'autre part, on a utilis des colonnes courtes (15 cm maximum) et des pressions de refoulement infrieures 50 bars, ce qui autorise l'emploi de chromatographes simplifis. Les dures des sparations sont au plus de 20 minutes.Eleven separations of pharmaceutical encountered in various formulations have been made by high speed adsorption liquid chromatography on spherosil-type silica, nominal diameter 5 m: noscapine-promethazine; mepyramine maleate-dextromethorphan hydrobromide; methyl and propyl p. hydroxybenzoates, amidopyrine and butazolidin; methaqualone and paracetamol; paraoxypropione, phenobarbital and methylthiouracil; benzocaine, procaine and tetracaine hydrochlorides; phenobarbital, papaverine hydrochloride and theophylline; phenobarbital, caffeine, amidopyrine and nicotinamide; biclotymol, neosynephrine hydrochloride, paracetamol and glycerol guaiacolate; lignocaine, hydrocortisone acetate and butazolidin. Except for the last all these separations are achieved by the isocratic mode with short columns (15 cm max.) and pressure less than 50 bars. Analysis time is always less than 20 minutes.
p-hydroxy methyl benzoate is fungistatic, in rather low concentrations, to pathogenic fungi. 0.1 %p-hydroxy methyl benzoate was required to inhibit growth ofCandida albicans andMonosporium apiospermum on a Sabouraud's agar medium.Trichophyton mentagrophytes, T. tonsurans, Geotrichum sp.,Sporotrichum schenckii, Blastomyces dermatitidis andCryptococcus neoformans failed to grow in the presence of 0.05 %p-hydroxy methyl benzoate. Growth ofEpidermophyton floccosum, Microsporum audouini, M. canis, M. gypseum, Trichophyton ferrugineum, T. rubrum, Hormodendrum compactum, H. Pedrosoi, Phialophora verrucosa, Nocardia asteroides, Coccidioides immitis, Haplosporangium parvum andHistoplasma capsulatum was suppressed by 0.025 % but not by 0.0125 % of this compound.
In vorliegender Arbeit wird die papierehromatographische Trennung und Identifizierung von vier Konservierungsmitteln beschrieben:
Äthyl- und Methylester der p-Hydroxybenzoesäure, die Benzoesäure und die Salicylsäure. Ferner wird eine Methode für die quantitative
Bestimmung des Äthylesters der p-Hydroxybenzoesäure angeführt. Das Prinzip dieser Methode besteht darin, daß nach vorangehender
Isolierung der Stoffe am Chromatogramm der Ester der p-Hydroxybenzoesäure unmittelbar am Papier mit einem für diesen Zweck
angefertigten Photometer bestimmt wird.
The interaction of methylparaben and propylparaben with bilirubin-albumin complexes was studied using difference spectra, Sephadex gel filtration, red blood cell uptake of bilirubin, and the peroxidase assay. Methylparaben was found to be a weak competitor with bilirubin for binding to primary albumin-binding sites but a strong binding competitor (similar to sulfisoxazole) at secondary sites. The displacing effects of methylparaben and sulfisoxazole were additive. Propylparaben bound to albumin but did not displace bilirubin. Drugs and injectable saline and water preparations which contain methylparaben should be avoided in jaundiced newborn infants when the high-affinity albumin-binding sites approach saturation.
The p-hydroxybenzoic acid and its methyl, ethyl, propyl, butyl, and benzyl esters are separated on thin layers of silanized silica gel using borated buffer (pH 11) as mobile phase, adding a given volume of organic solvent as required. The separation of the various compounds is complete and an accurated quantitative determination of the p-hydroxybenzoic acid and its esters is possible using a simple technique of elution and spectrophotometric determination.
By applying NMR spectrometry, a number of solutions containing unknown quantities of two or three alkyl p-hydroxybenzoates (parabens) in 60% polyethylene glycol in water were analyzed for quantification of the individual parabens. The method was found to be accurate, facile, and rapid and seems to possess a promising potential for applicability in related fields of pharmaceutical analysis.