Esters Of Parahydroxybenzoic Acid Research Articles

Determination of ointments active ingredients and parabens by one analytical method – capillary GC with cool-on-column injection and FID detection

In the field of quality control of medicines every pharmaceutical is tested for compliance with the requirements of the normative document for this drug to assess the quality. Among the quality indicators are the content of active ingredients and the excipients content. The more analytical methods used in a normative document, the greater the time and effort of people in all areas where a drug is developed, manufactured and controlled. A fast, precise, accurate and sensitive method has been developed for the simultaneous determination of the active ingredients of ointments of camphor, L-menthol, methyl salicylate, benzyl nicotinate, nonivamide, capsaicin, dihydrocapsaicin, nordihydrocapsaicin together with excipients, which are often para-hydroxybenzoic acid esters (parabens). The proposed gas chromatographic technique was validated. Good sensitivity for the application area (fractions of µg/mL for active ingredients and units of µg/mL for parabens), high reproducibility (relative standard deviation (RSD) doesn’t significantly exceed 2%) and the accuracy of the proposed method were demonstrated. The practical application was shown on the example of commercially available ointments. Also several assumptions about retention mechanism of such compounds were given. It seemed interesting to us for adapting proposed GC method to other components of ointments (or another dosage forms).

Read-across and new approach methodologies applied in a 10-step framework for cosmetics safety assessment – A case study with parabens

Parabens are esters of para-hydroxybenzoic acid that have been used as preservatives in many types of products for decades including agrochemicals, pharmaceuticals, food and cosmetics. This illustrative case study with propylparaben (PP) demonstrates a 10-step read-across (RAX) framework in practice. It aims at establishing a proof-of-concept for the value added by new approach methodologies (NAMs) in read-across (RAX) for use in a next-generation risk assessment (NGRA) in order to assess consumer safety after exposure to PP-containing cosmetics. In addition to structural and physico-chemical properties, in silico information, toxicogenomics, in vitro toxicodynamic, toxicokinetic data from PBK models, and bioactivity data are used to provide evidence of the chemical and biological similarity of PP and analogues and to establish potency trends for observed effects in vitro. The chemical category under consideration is short (C1–C4) linear chain n-alkyl parabens: methylparaben, ethylparaben, propylparaben and butylparaben. The goal of this case study is to illustrate how a practical framework for RAX can be used to fill a hypothetical data gap for reproductive toxicity of the target chemical PP.

Urinary Paraben Concentration and Its Association with Serum Triglyceride Concentration in 2013-2014 NHANES Participants: A Cross-Sectional Study

Background Alkyl esters of para-hydroxybenzoic acid, colloquially known as parabens, are types of preservatives found in multiple foodstuffs, pharmaceuticals, and personal care products to which Americans are exposed daily. It is unclear if parabens exhibit endocrine-disrupting properties. Parabens may interact with triglycerides in adipose tissue and impact lipid metabolism. Objective To evaluate the association between urinary paraben concentrations and serum triglyceride concentrations. Design A cross-sectional study. Setting. The Mobile Examination Centers affiliated with 2013-2014 NHANES. Participant(s). 827 adults (20 years or older) affiliated with the 2013-2014 NHANES. Intervention(s). None. Main Outcome Measure(s). Triglyceride levels were associated with urinary paraben concentrations (methyl, ethyl, and propyl) using a hierarchical multiple regression, adjusting for ethnicity/race, gender, BMI, and age. Unadjusted results are also reported. Results The geometric mean of the urinary concentration of methylparaben, ethylparaben, and propylparaben was 57.100, 2.537, and 6.537 ng/ml, respectively. Triglyceride concentrations were inversely associated with methylparaben (β = −0.092, P=0.07), ethylparaben (β = −0.066, P=0.045), and propylparaben (β = −0.076, P=0.025). Being female, non-Hispanic White, and non-Hispanic Black were associated with decreasing triglyceride levels in the presence of methylparaben, ethylparaben, and propylparaben, and age, BMI, and being male were associated with increasing circulating triglycerides. Conclusion Despite the potential detrimental effects of parabens on triglycerides, our results suggest that urinary excretions of methylparaben, ethylparaben, and propylparaben are associated with lower concentrations of circulating triglycerides in certain populations. Further research is needed to confirm the mechanisms and health impact of this relationship.

Weight and head circumference at birth in function of placental paraben load in Belgium: an ENVIRONAGE birth cohort study

BackgroundParabens are a group of esters of para-hydroxybenzoic acid utilized as antimicrobial preservatives in many personal care products. Epidemiological studies regarding the adverse effects of parabens on fetuses are limited. The aim of this study was to determine the association between placental paraben exposure and birth outcomes. We assessed paraben concentrations in placental tissue, which potentially gives a better understanding of fetal exposure than the maternal urinary concentrations which are the current golden standard.MethodsPlacental tissue was collected immediately after birth from 142 mother-child pairs from the ENVIRONAGE birth cohort. The placental concentrations of four parabens (methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)) were determined by ultra-performance liquid chromatography coupled with tandem mass-spectrometry. Generalized linear regression models were used to determine the association between paraben exposure levels and birth outcomes.ResultsThe geometric means of placental MeP, EtP, PrP, and BuP were 1.84, 2.16, 1.68 and 0.05 ng/g tissue, respectively. The sum of parabens (∑ parabens, including MeP, EtP and PrP) was negatively associated with birth weight in newborn girls (− 166 g, 95% CI: − 322, − 8.6, p = 0.04) after adjustment for a priori selected covariates. The sum of parabens was negatively associated with head circumference (− 0.6 cm, 95% CI: − 1.1, − 0.2, p = 0.008) and borderline associated with birth length (− 0.6 cm, 95% CI:-1.3, 0.1, p = 0.08). In newborn girls the placental concentration of EtP was negatively associated with head circumference (− 0.6 cm, 95% CI:-1.1, − 0.1, p = 0.01) and borderline significantly associated with birth weight and birth length. Lastly, placental EtP and ∑parabens were negatively associated with placental weight in newborn girls but not in newborn boys (− 45.3 g, 95% CI:-86.2, − 4.4, p = 0.03).ConclusionThe negative association between maternal paraben exposure and birth outcomes warrants further research and follow-up over time to determine long term effects of gestational exposure to parabens.

The sex-specific association between maternal paraben exposure and size at birth.

Parabens are a group of esters of parahydroxybenzoic acid and are utilized as antimicrobial preservatives in the majority of personal care products (PCPs). Epidemiological studies regarding the adverse effects of parabens on fetuses are still limited. The aim of this study was to determine the association between maternal paraben exposure and birth outcomes. One hundred and ninety-nine pregnant women were enrolled, and maternal urine was collected in the third trimester. The urine concentrations of four parabens (methyl (MP), ethyl (EP), propyl (PP), and butyl (BP)) were determined by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Generalized additive model-penalized regression splines and a multivariable regression model were employed to determine the association between paraben exposure levels and birth outcomes. A causal mediation analysis was conducted to determine the mediation effect of oxidative stress on birth outcomes. The geometric means of urinary MP, EP, PP, and BP were 51.79, 1.26, 4.21, and 1.25 μg/g cre., respectively. In the penalized regression splines, sex-specific associations between maternal MP levels and birth outcomes were observed; a downward curvature was observed between the MP level and birth weight, length, head circumference, and thoracic circumference among female newborns. Pregnant women in the group with MP levels above the third quartile had neonates with significantly lower body weight (β = -215.98 g, p value = 0.02) compared to those in the group with MP levels lower than the third quartile. No significant mediation of oxidative stress was observed between maternal MP exposure and female birth weight. The estimated proportion mediated ranged from -6% to 15%. The negative association between maternal paraben exposure and female birth outcomes in relation to child development should be carefully considered.

Urinary Paraben Concentrations and Its Association with Serum Triglyceride Concentrations in 2013–2014 NHANES Participants (P08-120-19)

ObjectivesAlkyl esters of para-hydroxybenzoic acid, colloquially known as parabens, are types of preservatives found in multiple foodstuffs, pharmaceuticals and personal care products to which Americans are exposed daily. It is unclear if parabens exhibit carcinogenic or endocrine-disrupting properties. Methylparaben and propylparaben, two of the parabens most commonly found in foods, may interact with triglycerides in adipose tissue and impact lipid metabolism. Due to the potential for adverse impact, it is imperative to study how parabens interact with lipids in humans. Our objective was to evaluate the association between urinary parabens and serum triglyceride concentrations. MethodsThis cross-sectional study used data from adults 20 years and older from the 2013–2014 NHANES. Triglyceride levels were associated with urinary paraben concentrations (methyl and propyl) using a Hierarchical Multiple Regression, adjusting for ethnicity/race, gender, waist circumference, BMI and age. ResultsA total of 794 participants were included in the analyses; their mean age was 49.7 years, 52.4% were female, 43.07% were white, and 20.2% were black. Triglycerides were inversely associated with methylparaben (CI 95% −.054, −.004, β = -0.82, P = 0.022) and propylparaben (CI 95% −.04, −.003, β = -0.81, P = 0.026). When adjusting for age, gender, race/ethnicity, BMI and waist circumference, the model remained significant for methylparaben (P < 0.05, adjusted R2 = .140), and propylparaben (P < 0.05, adjusted R2 = .140). ConclusionsDespite the potential detrimental effects of parabens on triglycerides, our results suggest that urinary excretion of methylparaben and propylparaben are associated with lower circulating triglycerides. Further research is needed to confirm the mechanisms and health impact of this relationship. Funding SourcesFlorida International University Internal Funding.

Assessment of hepatotoxicity and dermal toxicity of butyl paraben and methyl paraben using HepG2 and HDFn in vitro models

Parabens, esters of parahydroxybenzoic acid, are widely used in cosmetic, food and pharmaceutical industries mainly for their antibacterial and fungicidal properties. Methyl paraben has shown very low toxicity in a wide range of in vitro and animal tests. However, butyl paraben and derivatives, such as isobutyl parabens, are classified as allergens and have been shown to induce toxic effects. In the present study the effects of exposure to methyl or butyl paraben (5-1000 μM) on cytotoxicity, oxidative stress, mitochondrial dysfunction and genotoxicity were measured in a hepatocarcinoma cell line (HepG2) and human dermal fibroblasts neonatal (HDFn). Butyl paraben caused a concentration dependent decrease (above 400 μM) in cell viability for both cell lines. Toxicity of butyl paraben observed appeared to be mediated via ATP depletion as seen from luminescence assays. Depletion of glutathione was also observed for higher concentrations of butyl paraben, which may indicate the involvement of oxidative stress. Methyl paraben, however, did not show any significant decrease in cell viability, reduction in ATP or glutathione levels in HepG2 and HDFn cell lines at the concentrations tested. In vitro studies based on human cell lines can provide information in the early stages of multitier paraben toxicity studies and can be combined with in vivo and ex vivo studies to build more comprehensive, scientifically sound strategies for paraben safety testing.The results obtained in this study could supplement existing in vivo toxicity data for defining more robust limits for human exposure.

Transesterification of para-hydroxybenzoic acid esters (parabens) in the activated sludge

Hydrolysis is generally considered as the main pathway for the degradation of ester-type pollutants in aquatic environments. In this study, we found that when methanol or ethanol presented as the external carbon in the activated sludge, transesterification is very important for the degradation of para-hydroxybenzoic acid esters (parabens). In the activated sludge solutions with 1% methanol added, contribution of transesterification to the degradation of the propyl substituted paraben (PrP) and ethyl substituted paraben (EtP) accounted for 46% and 83%, respectively, in the early stage of the reaction. This indicates that in aquatic environments with alcohols presence, parabens prefer to form small molecule homologues than hydrolysis to acid. The predominant transesterification in the activated sludge is related to enzyme preference. Amano lipase from Pseudomonas fluorescens was verified to catalyze hydrolysis and transesterification of parabens, while the latter was dominant in water solution with 1% methanol or ethanol. Considering the common application of small molecular alcohols as the external carbon sources in wastewater treatment plants, transesterification might be an important pathway for the degradation of parabens pollutants in these engineering aquatic environments.

Parabens in human urine from several Asian countries, Greece, and the United States

Parabens, esters of para-hydroxybenzoic acid, are commonly used as antimicrobial preservatives in cosmetics and personal care products. Although several studies report exposure of humans to parabens in Western countries, little is known about exposure of humans to parabens in Asian countries. In this study, we determined concentrations of six parabens in spot urine samples collected from nine countries and estimated daily intakes (DI) and potential health risks of parabens. Ethyl-paraben, methyl-paraben, and propyl-paraben were detected frequently at 100, 98.0, and 80.3%, respectively, with representative median concentrations of 0.68, 7.02, and 1.21 ng/mL, respectively, for all nine countries. Urine samples from females (total median concentration: 32.3 ng/mL) contained significantly higher concentrations of parabens than did those from males (5.46 ng/mL). Urine samples from Korea (total median paraben concentration: 227 ng/mL) had the highest concentrations, which were one to two orders of magnitude higher than those found in other countries (3.67–29.1 ng/mL). The estimated DI of parabens (on the basis of concentrations measured in urine) varied widely, and several samples had propyl-paraben exposures above the acceptable DI. Our results suggest that paraben exposure is ubiquitous in Asian countries, and further assessment of potential health risk of these chemicals is needed.

Сравнительная характеристика составов стоматологических гелей, представленных на отечественном фармацевтическом рынке

In pharmacy organizations of the Russian Federation there are at least twelve names of dental gels and at least eight names of oral care products. All substances that are part of the soft medicinal forms can be divided into the following groups: active pharmaceutical substance, gellants, plasticizers, preservatives, flavoring agents, neutralizers, flavoring agents, etc. Lidocaine hydrochloride, chlorhexidine and various extracts are most often used as an active pharmaceutical substitute medicinal plants. For the formation of the gel base, it is preferable to use the slightly cross-linked acrylic polymers or cellulose derivatives. As preservatives, esters of para-hydroxybenzoic acid are used as mono-components, and in combination with other substances. Solvents are also an integral part of soft medicinal forms.

Occurrence and Profile Characteristics of the Pesticide Imidacloprid, Preservative Parabens, and Their Metabolites in Human Urine from Rural and Urban China.

Knowledge of human exposure to imidacloprid, the most extensively used insecticide, and para-hydroxybenzoic acid esters (parabens), the most extensively used preservative, is insufficient. In this study, 295 urine samples collected from subjects in rural and urban areas in China were analyzed for imidacloprid and four parabens (namely, methyl paraben, ethyl paraben, propyl paraben, and butyl paraben) as well as their major metabolites (namely, 6-chloronicotinic acid (6-ClNA) and para-hydroxybenzoic acid (p-HB)). Imidacloprid was detected in 100% of the urine samples from rural Chinese subjects and 95% of the urine samples from urban Chinese subjects. Concentrations of urinary imidacloprid detected in rural Chinese subjects (geometric mean (GM) = 0.18 ng/mL) were slightly higher than those detected in urban Chinese subjects (GM = 0.15 ng/mL) when the effect of pesticide spraying was excluded. However, concentrations of urinary imidacloprid detected in rural adults increased significantly in the subsequent days of pesticide spraying (GM = 0.62 ng/mL), which could return to the normal levels within 3 days. In contrast, concentrations of urinary parabens detected in rural Chinese subjects (GM = 6.90 ng/mL) were lower than that in urban Chinese subjects (GM = 30.5 ng/mL). In addition, the metabolism characteristics of imidacloprid to 6-ClNA and parabens to p-HB were discussed preliminarily.

Rapid determination of parabens in personal care products by stable isotope GC-MS/MS with dynamic selected reaction monitoring

In this study, a rapid and sensitive analytical method for the determination of methyl-, ethyl-, propyl-, and butyl esters of para-hydroxy benzoic acid (parabens) in personal care products was developed and fully validated. Test portions were extracted with methanol followed by vortexing, sonication, centrifugation, and filtration without derivatization. The four parabens were quantified by GC-MS/MS in the electron ionization mode. Four corresponding isotopically labeled parabens were selected as internal standards, which were added at the beginning of the sample preparation and used to correct for recovery and matrix effects. Sensitivity, extraction efficiency, and recovery of the respective analytes were evaluated. The coefficients of determination (r(2)) were all greater than 0.995 for the four parabens investigated. The recoveries ranged from 97 to 107% at three spiked levels and a one-time (single) extraction efficiency greater than 97% was obtained. This method has been applied to screen 26 personal care products. This is the first time that a unique GC-MS/MS method with dynamic selected reaction monitoring and confirmation of analytes has been used to determine these parabens in cosmetic personal care products.

Genotoxic and safety assessment of 2 parabens in somatic cells of in vivo Drosophila melanogaster

The objective of this study was to determine the possible genotoxic effects of the para-hydroxybenzoic acid esters (parabens) of methylparaben, propylparaben, and the mixed paraben groups formed by a combination of these, which are used as preservative substances in the food, cosmetic, and drug industries, on Drosophila melanogaster using the wing somatic mutation and recombination test (SMART). According to the data obtained from microscopic analysis, no increase was determined in the single type clone number at various concentrations (100, 150, 200, and 250 mM) of paraben groups in comparison with the control group. In addition, increases corresponding to the concentration increase in the single type and twin clone numbers were observed in the mixed paraben application group in comparison to the control group. However, this increase was not determined to create a statistically significant difference (P > 0.05). As a result of the data that we obtained, it has been concluded that parabens show toxic effects but no genotoxic effects on D. melanogaster.

131 EFFECT OF PARABENS ON THE DISRUPTION OF OVARIAN FOLLICLE MATURATION IN A NEONATAL FEMALE RAT MODEL

Parabens are widely used as an antimicrobial agent in the preparation of cosmetic consumer products and pharmaceuticals. Parabens are esters of para-hydroxybenzoic acid typically including methyl-, ethyl-, butyl-, isobutyl- and isopropyl-paraben. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In this study, we hypothesised that parabens might disrupt ovarian follicle maturation in female Sprague-Dawley rats during the neonatal period. A total of 55 female rats were divided into 11 groups, each composed of 5 rats. The pups were given daily subcutaneous injections of methyl-, propyl- or butyl-paraben at increasing concentrations of 62.5, 250, or 1000 mg kg–1 per day on neonatal Day 1 to 7. 17α-Ethinylestradiol (1 mg kg–1 per day) was used as a positive control. We examined the expression of anti-Müllerian hormone (AMH), which inhibits early folliculogenesis in the ovaries. Levels of AMH mRNA and protein were determined using real-time PCR and Western blot analysis, respectively. We found that the levels of AMH mRNA and protein were dose-dependently increased by methyl- and propyl-paraben compared with the vehicle. In particular, AMH mRNA and protein levels were markedly increased by parabens (methyl- and propyl-) at 1000 mg kg–1 per day. Data were analysed using a nonparametric one-way ANOVA followed by Dunnett's test for multiple comparisons. The ovaries were excised at postnatal Day 8 and fixed and stained with haematoxylin and eosin for histological analysis. The number of follicles were counted and classified into primordial, primary, or secondary stages via the largest serial sections at the centre of the ovary. Results showed that the total number of follicles and number of primordial follicles were increased by methyl- and propyl-parabens compared with the vehicle. Taken together, these results indicated that methyl- and propyl-parabens may have an estrogenic effect that disrupts the ovarian follicle development necessary for reproductive functions in a neonatal female rat model.

Food Additives and Allergic Diseases in Childhood

Many different additives include preservatives, stabili­ zers, conditioners, thickeners, colorings, flavorings, sweeteners, and antioxidants. Despite the multitude of additives known, only a small number has been associated with hypersensitivity reactions. A number of investigators have suggested that a significant population of patients with allergic diseases has symptoms related to the ingestion of food additives. However, the incidence and mechanism of reactions to additives in patients with chronic urticaria, angio­ edema, and atopic dermatitis remain unknown. A few studies of monosodium glutamate is reported to be associated with atopic dermatitis, but their relationship remains unknown. The best known dye is tartrazine. The group of azo dyes includes ponceau and sunset yellow. Amaranth (FD&C red no. 5) was banned from use in the US in 1975 because of claims related to carcinogenicity. Most of them are reported to be associated with aggravation of atopic dermatitis. 식품첨가물과 소아 알레르기질환 Food Additives and Allergic Diseases in Childhood Parabens are aliphatic esters of parahydroxybenzoic acid. Sodium benzoate is a closely related substance usually reported to cross­react with these compounds. These agents, which are widely used as preservatives in both food and drugs, are well recognized as causes of severe contact dermatitis. Additives would have to act as haptens to create a response mediated by IgE. The majority of these reactions are not of the immediate hypersensitivity type. Many cases of additive­pro­ voked urticaria or dermatitis occur as late as 24 hours after challenge, arguing against an IgE­mediated mechanism. In conclusion, the exact relationship between food additives and the allergic diseases still remains to be solved.

Comparative Study of the Determination of Parabens in Shampoos by Liquid Chromatography with Amperometric and Coulometric Detection

AbstractThe simultaneous determination of four para‐hydroxybenzoic acid esters (parabens) in shampoos was studied by liquid chromatography (LC) with amperometric (LC‐AD) and coulometric (LC‐CD) detection. The parabens were separated on an ODS C18 reversed column by isocratic elution with a mobile phase based on methanol‐0.1 M acetic acid (60 : 40%, v/v) with 0.02 M NaClO4 at a flow rate of 0.8 mL min−1. The limit of detection (S/N&gt;3) for the analytes was in the 15–25 pg (injected mass) range at an applied potential of 1.20 V vs. Ag/AgCl using the LC‐AD and in the 2–3 pg range at a potential of 0.790 V vs. Pd using the LC‐CD. The peak ratio of the internal standard peak (IS: 4‐hydroxybenzoic acid sec‐butyl ester) versus the analyte peak was found to be related to the amount injected from 0.1 ng to 100ng (r=0.996–0.999) with the LC‐AD and from 0.050 ng to 100 ng range (r=0.999–1.000) with the LC‐CD. The relative standard deviation (RSD, n=10) was comprised between 1.8 to 3.5% by LC‐AD ( 5 ng injected) and between 2.0 to 2.4% by LC‐CD (0.5 ng injected). The determination of four most used parabens in ten different shampoos was successfully realized.

Combining esters of para-hydroxy benzoic acid (parabens) to achieve increased antimicrobial activity

Lower alkyl esters of p-hydroxy benzoic acid (parabens) are widely used as preservatives of pharmaceuticals, cosmetics and allied products. Microbial activity increases with increasing alkyl chain length for the commonly used methyl, ethyl, propyl and butyl parabens, and synergy between parabens has been reported. However, although generally giving lower MIC values, greater toxicity issues seem to be associated with the larger parabens. Each of these observations is important in deciding how parabens should be combined to achieve best protection of the product in question, whilst minimizing the health risk to the user. The present study combined methyl (M)-, ethyl (E)-, propyl (P)- and butyl (B)-parabens in a matrix analysis to identify combinations of two or more parabens showing promising activity against microbes in vitro. Five particularly efficacious combinations were defined. Two of these were compared with a standard mixture of all four parabens widely used in the production of medicinals in Norway. Activities against a number of microbes in vitro, and in situ when included in an ophthalmic and a topical preparation were investigated. The novel combinations performed as well or better than the standard mixture in all tests when present at the same total paraben concentration. Two of the novel mixtures achieved in most tests a greater antimicrobial effect in vitro than a commonly used mixture at 50% of the total paraben concentration. It is concluded that the novel paraben mixtures 47% M, 23.5% E, 6.0% P, 23.5% B and 44.5% M, 44.5% P, 11.0% B at 0.05-0.1% w/v represent improvements on the widely used combination 50% M, 35% E, 10% P, 5% B within the framework of the current tests, and should be considered as alternatives.

Reaction of para-hydroxybenzoic acid esters with singlet oxygen in the presence of glutathione produces glutathione conjugates of hydroquinone, potent inducers of oxidative stress

The determination and toxicological characterization of products of the reaction between p-hydroxybenzoic acid esters (parabens) and singlet oxygen (1O2) are very important because of the frequent use of parabens in cosmetics and possible generation of 1O2 in the skin. We observed 1O2-dependent production of mono-, di-, and tri-substituted glutathione (GSH) conjugates of hydroquinone (HQ) during visible light-irradiation of a mixture of methyl or ethyl paraben and GSH in the presence of rose bengal (RB). 1,4-Benzoquinone (BQ) and HQ were produced during the irradiation in the absence of GSH. While a mixture of BQ and GSH produced only mono-substituted conjugate, irradiation of the mixture with RB produced mono-, di-, and tri-substituted conjugates. These observations indicate that 1O2 is involved both in the production of BQ and HQ from parabens and in the formation of multi-substituted GSH conjugates from mono-substituted conjugate. Tri-substituted conjugate generated larger amounts of hydrogen peroxide in an aqueous solution than mono-substituted conjugates or HQ did. Detection of semiquinone radical suggests that the autoxidation of conjugates is related to the generation of hydrogen peroxide. The results obtained in this study indicate that parabens may induce oxidative stress in the skin after conversion to GSH conjugates of HQ by reacting with 1O2 and GSH.

CALCULATION OF VAPOR PRESSURE CURVES FOR ETHYL, PROPYL, AND BUTYL PARABENS USING THERMOGRAVIMETRY

The heat treatment of parahydroxy benzoic acid esters follows zero order rate processes that are in good correlation with their evaporation process. Rising temperature experiments were performed and the optimum conditions were found when the heating rate was 10°C/min in an atmosphere of dry nitrogen, the flow rate of which was maintained at 100 mL/min. The Antoine constants for methyl paraben were substituted into the Antoine equation to get the corresponding vapor pressures that were then used in the Langmuir equation to obtain the value for the coefficient of evaporation k . The Eact value, obtained from the Arrhenius plot, was 75.1 kJ mol−1; the enthalpy of vaporization (ΔHvap) was calculated to be 77.9 kJ mol−1, in very close agreement with the Eact value. Using the Antoine and Langmuir equations, the value of k was experimentally determined to be 124525 ± 0.8, units being in the S.I. system. Taking the value of k to be independent of the substance, the corresponding vapor pressures were obtained for ethyl, propyl, and butyl parabens to give their vapor pressure plots. The thermogravimetric data was obtained for all the compounds under the same experimental conditions. Using the Clausius Clapeyron equation, the enthalpy of vaporization (ΔHvap) of ethyl, propyl, and butyl parabens were calculated to be 72.6, 76.5, and 72.2 kJ mol−1.

Sequential loss of outer membrane lipopolysaccharide and sensitivity of Escherichia coli to antibacterial agents

The effects of 3 phenolics and of a homologous series of esters of para-hydroxybenzoic acid (the parabens) on Escherichia coli with known deletions in outer membrane lipopolysaccharide (LPS) are described. Of the phenolics, chlorocresol was the most active and phenol the least, with butyl p-hydroxybenzoate the most effective paraben. The most sensitive strain to the various inhibitors was usually a deep rough mutant (heptoseless LPS). Studies were also made with a chelating agent, ethylenediamine tetraacetate (EDTA) in combination with some parabens. EDTA potentiated, to some extent, the activity of the methyl and butyl esters, its activity depending upon the concentration at which it was employed.