Article

Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum

Authors:
  • Prevent Breast Cancer Research Unit, Manchester, UK
  • Piraeus University of Applied Sciences
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Abstract

The concentrations of five esters of p-hydroxybenzoic acid (parabens) were measured using HPLC-MS/MS at four serial locations across the human breast from axilla to sternum using human breast tissue collected from 40 mastectomies for primary breast cancer in England between 2005 and 2008. One or more paraben esters were quantifiable in 158/160 (99%) of the tissue samples and in 96/160 (60%) all five esters were measured. Variation was notable with respect to individual paraben esters, location within one breast and similar locations in different breasts. Overall median values in nanograms per gram tissue for the 160 tissue samples were highest for n-propylparaben [16.8 (range 0-2052.7)] and methylparaben [16.6 (range 0-5102.9)]; levels were lower for n-butylparaben [5.8 (range 0-95.4)], ethylparaben [3.4 (range 0-499.7)] and isobutylparaben 2.1 (range 0-802.9). The overall median value for total paraben was 85.5 ng g(-1) tissue (range 0-5134.5). The source of the paraben cannot be identified, but paraben was measured in the 7/40 patients who reported never having used underarm cosmetics in their lifetime. No correlations were found between paraben concentrations and age of patient (37-91 years), length of breast feeding (0-23 months), tumour location or tumour oestrogen receptor content. In view of the disproportionate incidence of breast cancer in the upper outer quadrant, paraben concentrations were compared across the four regions of the breast: n-propylparaben was found at significantly higher levels in the axilla than mid (P = 0.004 Wilcoxon matched pairs) or medial (P = 0.021 Wilcoxon matched pairs) regions (P = 0.010 Friedman ANOVA).

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... The alkyl esters of p-hydroxybenzoic acid (parabens) are added as preservatives to personal care products, pharmaceuticals and foods [1] . Of the five commonly used esters (methylparaben, ethylparaben, n-propylparaben, n-butylparaben and isobutylparaben) 99% of the human breast tissues were found to contain at least one of the esters, and 60% contained all five esters [26] . Although the parabens bind more weakly to estrogen receptors than do the endogenous estrogens, their efficacy is not weak provided sufficient concentration is present [27] . ...
... Although the parabens bind more weakly to estrogen receptors than do the endogenous estrogens, their efficacy is not weak provided sufficient concentration is present [27] . It is therefore noteworthy that the concentrations of parabens measurable to human breast tissues are considerably higher (in the micromolar range) [26] than the levels of endogenous 17b-estradiol (in the nanomolar range) [2,28] . Previous work has demonstrated that parabens can increase proliferation of estrogen-responsive human breast cancer cells in cell culture at concentrations measurable in some human breast tissue samples [29] through estrogen receptor-mediated mechanisms [27] . ...
... Even mixtures of the different esters of parabens can add together to give increased cell proliferation [29] . This is relevant environmentally where human breast tissue samples were found to contain differing levels of the individual paraben esters [26] and implies that the same outcomes can arise from different mixtures of estrogen disrupting chemicals [29] . Clearly in ER-mediated mechanisms, such as in increasing cell proliferation, each chemical will act according to its relative estrogen receptor binding affinity but low doses of different chemicals can add together until a maximum proliferative signal is achieved. ...
Article
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Estrogen disrupting chemicals are environmental compounds which mimic, antagonize or interfere in the action of physiological estrogens. They occur naturally (plant phytoestrogens) but the majority are man-made compounds, which, through their use in agricultural, industrial and consumer products, have become widely present in human tissues including breast tissue. Since exposure to estrogen is a risk factor for breast cancer, estrogen disrupting chemicals may also contribute to breast cancer development. This review discusses evidence implicating estrogen disrupting chemicals in increasing migratory and invasive activity of breast epithelial cells, in epithelial-to-mesenchymal transition, and in growth of breast tumours at metastatic sites as well as the primary site. Mechanisms may be through the ability of such chemicals to bind to estrogen receptors, but unlike for proliferation, effects on cell migration and invasion are not limited to estrogen receptor-mediated mechanisms. Furthermore, whilst effects on proliferation can be measured within hours/days of adding an estrogen disrupting chemical to estrogen-responsive breast cancer cells, effects on cell migration occur after longer times (weeks). Most studies have focused on individual chemicals, but there is now a need to consider the environmentally relevant effects of long-term, low-dose exposure to complex mixtures of estrogen disrupting chemicals on mechanisms of metastasis.
... To establish links between parabens and breast cancer, it is imperative to demonstrate the presence and localization of parabens within the breast tissue. Paraben levels in breast tissue extracted from axilla to sternum have been investigated [11,32]. MP was detected at approximately 16.6 ng per gram of the breast tissue, higher than previously documented [19]. ...
... However, no significant correlation was identified between the concentration of parabens and the location of breast tumors or the estrogen receptor status in the breast tumors. It has been shown that parabens have greater bioaccumulation within the outer areas (axilla and lateral) of the breast than the inner areas (mid and medial) [32]. The outer areas of the breast consist of more adipose tissue where the mammary glands are centrally located. ...
... Moreover, the detection and accumulation of parabens in the adipose tissue of the breast have been reported, possibly due to their moderate hydrophobicity [23]. Higher levels of parabens detected in the outer regions of the breasts might be associated with how deodorants are applied [32]. ...
There is increasing recognition that environmental exposure to chemicals, such as endocrine-disruptive chemicals (EDCs), contributes to the development of breast cancer. Parabens are a group of EDCs commonly found in personal care products, foods, and pharmaceuticals. Systemic exposure to parabens has been confirmed by the ubiquitous detection of parabens in human blood and urine samples. Although evidence from in vivo and epidemiological studies linking parabens exposure to breast cancer is limited, the current evidence suggests that parabens may negatively interfere with some endocrine and intracrine targets relevant to breast carcinogenesis. So far, most studies have focused on a single paraben's effects and the direct modulating effects on estrogen receptors or the androgen receptor in vitro. Recent studies have revealed that parabens can modulate local estrogen-converting enzymes, 17β-hydroxysteroid dehydrogenase 1 and 2 and increase local estrogen levels. Also, parabens can crosstalk with the human epidermal growth factor receptor 2 (HER2) pathway and work with ER signaling to increase pro-oncogenic c-Myc expression in ER+/HER2+ breast cancer cells. Future studies investigating paraben mixtures and their crosstalk with other EDCs or signaling pathways both in vitro and in vivo in the context of breast cancer development are warranted.
... Another review article provided by Darbre and Harvey, 2008 repeated the arguments that have been refuted and new data or evidence were not added [20]. A study provided by Barr et al. (2012) [56] showed that in different regions of healthy breast tissue, the concentration of different parabens was similar in different breast regions, except for PP, which was detected at higher levels in the upper outer quadrant of the breast. In 40 patients that participated in the study, seven of them had never used deodorants or other products for the underarm. ...
... Another review article provided by Darbre and Harvey, 2008 repeated the arguments that have been refuted and new data or evidence were not added [20]. A study provided by Barr et al. (2012) [56] showed that in different regions of healthy breast tissue, the concentration of different parabens was similar in different breast regions, except for PP, which was detected at higher levels in the upper outer quadrant of the breast. In 40 patients that participated in the study, seven of them had never used deodorants or other products for the underarm. ...
... In 40 patients that participated in the study, seven of them had never used deodorants or other products for the underarm. This study also concludes that there are no correlations between paraben concentrations and age of patient, length of breast feeding, tumor location or tumor oestrogen receptor content [20,56]. ...
Article
Full-text available
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.
... [18,19] P.D. Dabre et al. and Barr et al. reported the measurement of parabens in breast tumours and in human breast tissue at serial locations of the breast form axilla to sternum. [20,21] Recently, two research groups investigated the presence of parabens in female urine and breast tissue samples, cancerous and healthy, from women in Croatia. [22,23] The documented bioaccumulation of parabens has raised many health concerns since their presence s both in high levels and in certain ...
... This statement is strongly supported by the measurement of parabens as intact esters in human breast tissues and in breast carcinoma. [20,21,23,27,28] This accumulation has been directly connected to body care and underarm cosmetics. Estrogenic activity increases concurrently with the elongation and the branching of the alkyl chain, while the aromatic ring in BzPB also augments estrogenicity. ...
... On the contrary, in case of blood and human milk, due to the increase of interferences, extra parameters and steps should be considered and applied such as precipitation, centrifugation etc In general, tissue analysis is by far the most laborious task, requiring extra steps, time and skills in order to handling and pretreating solid tissue samples. [20,21,23] This is maybe one of the reasons for the observed shortage of published surveys referring to this target matrix, despite the augmented toxicological interest for that. Specifically, a well-designed homogenization process should be included for delivering parabens from the solid stuff to the liquid homogenate solution, before the application of the proper extraction, cleaning and preconcentration technique, in order to selectively isolate parabens from the total solid extracts. ...
Article
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.
... For example, tests in animals showed an increase in uterine weight in immature rats, after exposure to parabens, while male rodents also exhibited a decrease in testosterone secretion and some changes in the reproductive organ after exposure to this substance [16]. In humans, parabens are detected in blood, milk, urine [17] and also in breast tumor tissues [15,18]. ...
... Thus, the production of chlorine, hypochlorite/hypochlorous acid is expected (Eqs. [17][18][19], as well as the presence of peroxo-sulfates (Eq. 20) in the aqueous medium, which can contribute to the degradation of organic pollutant present in the reaction system. ...
Article
Endocrine disruptors are often reported in the literature as recalcitrant pollutants in aquatic ecosystems. For this reason, the present study focused on advanced oxidation processes, including Fenton, photo-Fenton, electro-Fenton (EF), and electrochemical oxidation (EO) as an alternative to the degradation of Methylparaben (MeP) from aqueous media. The degradation of MeP by Fenton based processes was completed in 20 minutes under optimal conditions (16 mg L⁻¹ Fe²⁺ and 62 mg L⁻¹ H2O2), while for the Photo-Fenton process by a reactor with a 4 W UV lamp, 4 mg L⁻¹ Fe²⁺ and 52 mg L⁻¹ H2O2, the complete degradation was attained within 16 minutes. Interestingly, outstanding results were achieved in the Electro-Fenton process carried out in a reactor equipped with a Ti/Ru0,3Ti0,7O2 as a cathode and a platinum anode, which, under optimized conditions (i.e. 4 mg L⁻¹ Fe²⁺, j = 25 mA cm⁻² and 0.05 mol L⁻¹ Na2SO4) only 10 minutes was required to completely remove the contaminant from both synthetic and tap water. The MeP removal followed pseudo-first-order reaction kinetics in the following order: Electrochemical oxidation (EO) < Fenton < photo-Fenton < electro-Fenton (EF). Finally, after a comparison with the available literature concerning the oxidation of MeP, the EF system here proposed is presented as among the best in removal rate and mineralization as compared with other AOPs, performing better even in real water matrices.
... Yapılan çalışmalarda bu türevlerin insan dokularında ve vücut sıvılarında da tespit edildiğini göstermektedir. Ancak bilim dünyasında endişe uyandıran kısım, meme kanserli hastaların meme dokusunda parabenin tespit edilmesidir [47,48]. Bu nedenle, özellikle son yıllarda kozmetik ürünlerdeki kullanımı kamuoyunda endişe uyandırmış ve bu nedenle "paraben free" ürünler pazarlama stratejisi ile piyasada yer almaya başlamıştır. ...
... Elde edilen veriler doğrultusunda, yüksek oranda paraben içeren kozmetik preparatların kullanılmasının, sağlık üzerinde olumsuz etkiler gösterebileceği belirtilmiştir [45]. Kozmetik ürünler aracılığıyla paraben maruziyetinin bir sonucu olarak östrojenik etkilerin görülme riski sebebiyle, bu koruyucuları içeren kozmetik ürünlerinin eş zamanlı olarak kullanımından kaçınılmalıdır [45,48]. Bununla birlikte, parabenlerin sağlık üzerindeki etkilerini araştıran çalışmalar hala çelişkilidir. ...
... In animal studies, parabens have been shown to affect both male and female reproductive developments (Oishi 2001;Kang et al. 2002;Kawaguchi et al. 2009;Vo et al. 2010;Ahn et al. 2012;Guerra, Sanabria, Cagliarani, et al. 2017;Fisher et al. 2020). In humans, parabens have been detected in normal breast cells and maternal urine and breast milk (Barr et al. 2012;Fisher et al. 2017;Amin et al. 2019). These studies have revealed that the estrogenic properties of parabens may perturb the mechanism of normal breast cells and potentially contribute to their abnormal growth and thus increase the risk of the breast cancer (Barr et al. 2012;Fisher et al. 2017;Amin et al. 2019). ...
... In humans, parabens have been detected in normal breast cells and maternal urine and breast milk (Barr et al. 2012;Fisher et al. 2017;Amin et al. 2019). These studies have revealed that the estrogenic properties of parabens may perturb the mechanism of normal breast cells and potentially contribute to their abnormal growth and thus increase the risk of the breast cancer (Barr et al. 2012;Fisher et al. 2017;Amin et al. 2019). By far there are only one epidemiological study that reported the association of paraben exposures and breast cancer risk and mortality following breast cancer (Parada et al. 2019). ...
Article
Background Endocrine-disrupting compounds (EDCs) are ubiquitous substances that are found in our everyday lives, including pesticides, plasticizers, pharmaceutical agents, personal care products, and also in food products and food packaging. Increasing epidemiological evidence suggest that EDCs may affect the development or progression of breast cancer and consequently lead to lifelong harmful health consequences, especially when exposure occurs during early life in humans. Yet so far no appraisal of the available evidence has been conducted on this topic. Objective To systematically review all the available epidemiological studies about the association of the levels of environmental exposures of EDCs with breast cancer risk. Methods The search was performed in accordance with the PRISMA guidelines. We retrieved articles from PubMed (MEDLINE) until 10 March 2021. The key words used in this research were: “Endocrine disruptor(s)” OR “Endocrine disrupting chemical(s)” OR any of the EDCs mentioned below AND “Breast cancer” to locate all relevant articles published. We included only cohort studies and case-control studies. All relevant articles were accessed in full text and were evaluated and summarized in tables. Results We identified 131 studies that met the search criteria and were included in this systematic review. EDCs reviewed herein included pesticides (e.g. p,p’-dichlorodiphenyltrichloroethane (DDT), p,p’-dichlorodiphenyldichloroethylene (DDE), atrazine, 2,3,7,8-tetrachloridibenzo-p-dioxin (TCDD or dioxin)), synthetic chemicals (e.g. bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), parabens, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), contraceptive pills), phytoestrogens (e.g. genistein, resveratrol), and certain mycotoxins (e.g. zearalenone). Most studies assessed environmental EDCs exposure via biomarker measurements. Conclusion We identified certain EDC exposures could potentially elevate the risk of breast cancer. As majority of EDCs are highly persistent in the environment and bio-accumulative, it is essential to assess the long-term impacts of EDC exposures, especially multi-generational and transgenerational. Also, since food is often a major route of exposure to EDCs, well-designed exposure assessments of potential EDCs in food and food packing are necessary and their potential link to breast cancer development need to be carefully evaluated for subsequent EDC policy making and regulations.
... Methylparaben, an example of a compound that belongs to the class of parabens, may be found in urine samples from 99.1% of Americans; mammalian breast tissue & breast milk are also included. [68,69] The results imply that paraben exposure affects the differentiation & multiplication of breast stem cells. On the other hand, with greater research focusing on changes, it would be desirable to have more stem cells in number. ...
... 3,4 Their estrogenic effect was assumed to be able to cause breast cancer. 5,6 In addition, some negative impacts on the male reproductive system were reported. 7 In the light of the related researches, parabens are classified as suspected endocrine disruptors and suspected carcinogens. ...
... Methylparaben, an example of a compound that belongs to the class of parabens, may be found in urine samples from 99.1% of Americans; mammalian breast tissue & breast milk are also included. [68,69] The results imply that paraben exposure affects the differentiation & multiplication of breast stem cells. On the other hand, with greater research focusing on changes, it would be desirable to have more stem cells in number. ...
Article
Full-text available
Cancer alludes to over 277 distinct malignancies in its broadest sense. The pathogenesis of these cancers has uncovered various cancer stages in which gene mutations will play a key role. Abnormal multiplication of cells occurs due to these mutations in the genes. Environmental factors are thought to be responsible for 70-90 percent of all carcinomas. A tissue with a large number of stem cells is considered a sign of developing carcinoma in that particular tissue. The characterization of tumors is done by obtaining stem cell-like properties, which shows evidence that a stem cell-like population endures and proliferates tumors. Finding people who appear healthy in a community, have a disease in its earliest stages, or are more likely to get a condition is known as screening in the healthcare industry. An early diagnosis of an illness, which can subsequently be efficiently treated at an early stage, results in a decreased disease-specific or overall fatality. This is the aim of a screening test. In this, the effects of different environmental exposures that may impair functions of stem cells related to carcinogenesis. Several cancer screening methods were identified in the mid of the 20 th century. In this article, we have discussed the effectiveness and evaluation of the screening of cancer programs in different countries. This article also established the estimated number of deaths and new cases observed worldwide in 2018. In this review, we have also established the molecular perspectives of cancer. The economic constraints related to the screening problems are also discussed.
... Parabens have been detected in a broad range of human tissues, as well as urine and hair samples (Barr et al., 2012;Moos et al., 2014;Hines et al., 2015;Hajizadeh et al., 2020;Song et al., 2020;Nowak et al., 2021a ;Zhu and Kannan, 2020;Wojtkiewicz et al., 2021). Several studies have demonstrated an association between maternal and fetal exposures to parabens, and their possible association with birth outcomes (Pycke et al., 2015, Geer et al., 2017, Wu et al., 2017, Chang et al., 2019, Vrijens et al., 2020Song et al., 2020;Wen et al., 2020;Karzi et al., 2021;Sunyer-Caldú et al., 2021). ...
Article
Full-text available
Parabens are a category of antimicrobial preservatives that may play a role in the etiology and epidemiology of cancers. Parabens are employed in a wide range of pharmaceuticals, cosmetics, personal care products, and processed foods. Parabens are thought to influence the evolution of carcinogenesis in breast cancer by acting as genotoxicants, cell proliferation factors, migratory and metastatic activators, and hyper-accumulate in breast cancer cells. A goal of this study was to characterize the relationship between paraben contamination and the incidence of both malignant and benign breast tumors in patients attending Hojati and Khanavadeh hospitals, in the city of Isfahan, Iran. A second goal was to examine the relationship among methyl, ethyl, n-propyl, and n-butyl paraben concentrations, exposure factors for parabens, and risk factors for breast cancer among patients with cancerous and non-cancerous breast tissues. A reference for mean concentration of total parabens in healthy, non-tumor tissue is 21 ng/g. In this study, benign breast tumors had a mean concentration of 357 ng/g of total parabens. In contrast, malignant breast tissue had a mean concentration of 472 ng/g(mean) total parabens. Malignant tumors had higher n-propyl paraben (β=39.52; p=0.039) and n-butyl paraben (β=43.92; p=0.028) concentrations among the patients with a positive human epidermal growth factor receptor2 (HER2) rather than the patients with a negative HER2. Results indicated that higher age was associated with higher n-butyl paraben concentration (β=1.97; p=0.012) among the patients with malignant tumors. Moreover, the body mass index (BMI) had a positive relationship with ethyl paraben concentration (β=6.37; p= 0.030) among patients with malignant tumors. The questionnaire-survey used in this study was unable to discern why there was higher accumulation of parabens in the tumor-tissue types. Larger population-based longitudinal studies are necessary to confirm this association and to evaluate the association of parabens with clinical indicators of breast cancer and mortality.
... In pharmaceutical preparations, the content of parabens, only sporadically, may exceed 1% [10]. Many toxicological studies were focused on monitoring of a content of parabens in human urine [11], and breast tissues [12], which is associated with the observed adverse effects on male reproduction in animals [11], and hypotheses on connection of parabens with a breast cancer in woman [13][14][15]. The intensity of conducting the analytical, environmental and toxicological studies of parabens can be also attributed to a large volume of their production, which in the European Union countries is estimated as 10,000 tons per annum [16]. ...
Article
The methyl ester of p-hydroxybenzoic acid (methylparaben, MP) is commonly used as a preservative in cosmetics, food and pharmaceuticals. Its widely examined interactions with aqueous system and human organisms prove a necessity of the monitoring of its release to natural environment and the efficiency of its removal from waters and wastewaters. In this work, the yield of MP decomposition in aqueous solutions by gamma-radiation was investigated under oxidative conditions. The LC/MS, GC/MS and ion-chromatography were employed for examination of the yield of MP decomposition in function of the absorbed dose of radiation and for identification of stable products derived from MP formed during radiolysis prior to its complete mineralization. The studies were carried out in aerated aqueous solutions and under conditions with the predominance of OH radicals. The mechanisms of radical reactions were proposed leading to formation of the identified stable products. The irradiation of aerated MP solutions was assumed as a more favorable condition in terms of the yield of MP decomposition and a lack of changes of cytotoxicity towards 3 human cell lines was found. Under such conditions a 90% decomposition of MP at initial concentration 0.5 mg L⁻¹ was observed for 100 Gy absorbed dose, which for the employed ⁶⁰Co γ -source took 3.3 min. This provides a much better efficiency of MP decomposition in comparison to most of developed AOPs for this purpose.
... In pharmaceutical preparations, the content of parabens, only sporadically, may exceed 1% [10]. Many toxicological studies were focused on monitoring of a content of parabens in human urine [11], and breast tissues [12], which is associated with the observed adverse effects on male reproduction in animals [11], and hypotheses on connection of parabens with a breast cancer in woman [13][14][15]. The intensity of conducting the analytical, environmental and toxicological studies of parabens can be also attributed to a large volume of their production, which in the European Union countries is estimated as 10,000 tons per annum [16]. ...
... In that framework, endocrine-disrupting compounds (EDCs) have been in the spotlight in the last decade since they can interfere with the endocrine system leading to, for instance, mutagenic, carcinogenic or hepatotoxic effects [6]. Some examples concerning EDCs include (i) bisphenols [7][8][9], (ii) benzophenones [10,11], (iii) parabens [12][13][14], (iv) phthalates [15,16] and (v) organochlorides such as triclosan (TCS) and triclocarban (TCC) [17][18][19]. ...
Article
Full-text available
In the present work, a target analysis method for simultaneously determining 24 diverse endocrine-disrupting compounds (EDCs) in urine (benzophenones, bisphenols, parabens, phthalates and antibacterials) was developed. The target analysis approach (including enzymatic hydrolysis, clean-up by solid-phase extraction and analysis by liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS)) was optimized, validated and applied to volunteers’ samples, in which 67% of the target EDCs were quantified. For instance, benzophenone-3 (0.2–13 ng g ⁻¹ ), bisphenol A (7.7–13.7 ng g ⁻¹ ), methyl 3,5-dihydroxybenzoate (8–254 ng g ⁻¹ ), mono butyl phthalate (2–17 ng g ⁻¹ ) and triclosan (0.3–9 ng g ⁻¹ ) were found at the highest concentrations, but the presence of other analogues was detected as well. The developed target method was further extended to suspect and non-target screening (SNTS) by means of LC coupled to high-resolution MS/MS. First, well-defined workflows for SNTS were validated by applying the previously developed method to an extended list of compounds (83), and then, to the same real urine samples. From a list of approximately 4000 suspects, 33 were annotated at levels from 1 to 3, with food additives/ingredients and personal care products being the most abundant ones. In the non-target approach, the search was limited to molecules containing S, Cl and/or Br atoms, annotating 4 pharmaceuticals. The results from this study showed that the combination of the lower limits of detection of MS/MS and the identification power of high-resolution MS/MS is still compulsory for a more accurate definition of human exposome in urine samples. Graphical abstract
... The first use of parabens was made in the mid-1920 s in pharmaceuticals but now is widely used in cosmetics (Nowak et al., 2018). They are considered a non-persistent pollutant in the environment but are usually found in breast tumour and adipose tissue (Barr et al., 2012;Artacho-Cordón et al., 2018). MeP was detected in high concentration (in a range between 0.21 and 242 ng/L) in the surface water (Czarczyńska-Goślińska et al., 2017;Chen et al., 2018;Marta-Sanchez et al., 2018;Song et al., 2020). ...
Article
Personal care products (PCPs) are part of the large and growing family of emerging contaminants (ECs). Many daily products such as sunscreens, toothpaste, make-up products, perfume, and others, fall under this definition, and their use is increasing exponentially. Furthermore, the degradation of some components of these products is limited. Indeed, they are able to easily reach and accumulate in aquatic systems, representing a new class of contaminants. Moreover, due to their chemical properties, they can interfere at different biological levels, and for this reason, they need to be thoroughly investigated. We have reviewed the literature on PCPs, with a special focus on the adverse effects on the freshwater zebrafish (Danio rerio). The aim of this work is to provide a careful assessment of the toxicity of these compounds, in order to raise awareness for more conscious and responsible use.
... A number of studies have reported that parabens act mainly by an in-vivo mechanism mediated by the estrogen receptor. 23 Parabens have been identified as weak estrogens because of their low-binding affinity to the estrogen receptor, but they can give the same magnitude of response on the growth of human breast cancer cells in-vitro as 17β-estradiol when adequate concentrations are present. 24 Ethylene oxide is widely used in shampoo, fragrances, detergents, thickeners etc. ...
... Parabens have also been considered to be factors that may influence the occurrence of breast cancer in women (Harvey and Darbre, 2004). Significant levels of parabens have been detected in different biological samples (urine, plasma, breast tissues, etc.) from various populations (Barr et al., 2012;Frederiksen et al., 2011;Shirai et al., 2013). ...
Article
Objective Parabens are extensively used, and cause widespread exposure of the general population including pregnant women and developing fetuses to these pollutants. In this study, we aimed to investigate the association between the maternal exposure of parabens to study their transfer passed through the placental barrier to amniotic fluid; the second objective was to determine the association of paraben concentration in the amniotic fluid with the offspring birth size. Methods This cross-sectional study was conducted from June 2019 to March 2021 in Isfahan, Iran. Samples of amniotic fluid were collected as set from 128 pregnant women at Cesarean section. The amniotic fluid concentrations of four parabens including methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP) were determined using gas chromatography tandem mass spectroscopy (GC-Mass). Results The pointed parabens were extracted from yielded clear supernatant using a dispersive liquid–liquid microextraction (DLLME) method. Four paraben derivatives including MP (normal: 0.68 ± 0.7; overweight: 1.40 ± 1.76; obese: 0.30 ± 0.26; p-value: 0.275), EP (normal: 0.14 ± 0.09; overweight: 0.72 ± 0.72; obese: 0.38 ± 0.05; p-value: 0.434), PP (normal: 0.05 ± 0.05; overweight: 0.06 ± 0.06; obese: 0.20 ± 0.17; p-value: 0.770), and BP (normal: 2.89 ± 1.80; overweight: 3.89 ± 6.48; obese: 5.80 ± 7.56; p-value: 0.341) were simultaneously detected in samples of maternal amniotic fluid using GC–MS. In 92.2% (n = 118) of pregnant women, the paraben derivatives (MP, EP, PP, BP) were detected. We found that considerable levels of MP, EP, PP, and BP existed in 22.6% (n = 29), 21.9% (n = 28), 29.7% (n = 38), and 85.2% (n = 109) of samples, respectively. In addition, the correlation between paraben concentrations in amniotic fluid and birth size was investigated. The results showed that an inverse significant association between MP and head circumference, chest, hip, and arm circumference. While a positive correlation between MP and height of newborn was observed. Similar correlations were observed for EP and weight, height, head circumference, chest, hip, and arm. Conclusion The current study indicated that parabens have been detected in amniotic fluid samples and a strong/possible correlation between exposure of pregnant women to parabens and the birth size of newborns.
... We also report that higher levels of EP and PB in the urine samples are consistent with the increase in the severity, especially in the older population of 65 years and older, with higher BMI and high lipid concentrations in the blood. The association of EP and PB and PCa effect was correlated with some selected variables, such as age, weight, BMI, and lipids concentration, as supported by previous studies [43,[97][98][99][100][101], enhancing the PCa risks in the subjects. In this risk assessment approach, we innovatively used the curated in silico information on differential gene expressions, pathways, and genetic networks of PCa on various databases: TCGA, GO, GEO, KEGG, DAVID, CTD, Cytoscape, and UALCAN. ...
Article
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Prostate cancer (PCa) is one of the leading malignant tumors in US men. The lack of understanding of the molecular pathology on the risk of food supply chain exposures of environmental phenol (EP) and paraben (PB) chemicals limits the prevention, diagnosis, and treatment options. This research aims to utilize a risk assessment approach to demonstrate the association of EP and PB exposures detected in the urine samples along with PCa in US men (NHANES data 2005–2015). Further, we employ integrated bioinformatics to examine how EP and PB exposure influences the molecular pathways associated with the progression of PCa. The odds ratio, multiple regression model, and Pearson coefficients were used to evaluate goodness-of-fit analyses. The results demonstrated associations of EPs, PBs, and their metabolites, qualitative and quantitative variables, with PCa. The genes responsive to EP and PB exposures were identified using the Comparative Toxicogenomic Database (CTD). DAVID.6.8, GO, and KEGG enrichment analyses were used to delineate their roles in prostate carcinogenesis. The plug-in CytoHubba and MCODE completed identification of the hub genes in Cytoscape software for their roles in the PCa prognosis. It was then validated by using the UALCAN database by evaluating the expression levels and predictive values of the identified hub genes in prostate cancer prognosis using TCGA data. We demonstrate a significant association of higher levels of EPs and PBs in the urine samples, categorical and numerical confounders, with self-reported PCa cases. The higher expression levels of the hub genes (BUB1B, TOP2A, UBE2C, RRM2, and CENPF) in the aggressive stages (Gleason score > 8) of PCa tissues indicate their potential role(s) in the carcinogenic pathways. Our results present an innovative approach to extrapolate and validate hub genes responsive to the EPs and PBs, which may contribute to the severity of the disease prognosis, especially in the older population of US men.
... Epidemiological evidence also exists linking paraben exposure to breast cancer development. Parabens have been detected in breast tissue, including breast tumor tissue (88)(89)(90)(91). Furthermore, parabens have been detected in urine and plasma samples from women with breast cancer (92,93). ...
Article
Full-text available
Endocrine-disrupting chemicals (EDCs) are known contributors to breast cancer development. EDC exposures commonly occur through food packaging, cookware, fabrics, and personal care products as well as through the environment. Increasing evidence highlights disparities in EDC exposure across racial/ethnic groups, yet breast cancer research continues to lack the inclusion necessary to positively impact treatment response and overall survival in these socially disadvantaged populations. Additionally, the inequity in environmental exposures has yet to be remedied. Exposure to EDCs due to structural racism poses an unequivocal risk to marginalized communities. In this review, we summarize recent epidemiological and molecular studies on two lesser-studied EDCs, per- and polyfluoroalkyl substances (PFAS) and parabens, the health disparities that exist in EDC exposure between populations and their association with breast carcinogenesis. We discuss the importance of understanding the relationship between EDC exposure and breast cancer development, particularly to promote efforts to mitigate exposures and improve breast cancer disparities in socially disadvantaged populations.
... The estrogenic effects of parabens such as methylparaben, ethylparaben, n-propylparaben and n-butylparaben have been reported in estrogen-sensitive MCF7 human breast cancer cells as well as in other lines of human breast cancer cells [1,14,15]. Additionally, their accumulation in human breast tissue [16,17] indicates their potential to drive the sustained proliferation of ER +ve breast epithelial cells. Parabens are full agonists with the same efficacy as estradiol when available at high concentrations, as it increases proliferation of human breast cancer cells to about the same level, where the maximal cell yield attained was with 3 × 10 −11 M. ...
Article
Full-text available
Methylparaben (MP) is the most commonly used preservative in various everyday life products. It is considered one of the xenoestrogens because of its metabolic activity as an estrogen agonist. Hence, it is implicated to play a role in breast cancer development. The human breast adenocarcinoma cell line MCF-7 (Michigan Cancer Foundation-7) is used as a standard model for in vitro cancer research. However, it is now recognized that MCF-7 is heterogeneous concerning both the expression of hormone receptors and the utilization of the signaling pathways linked to these receptors. The present study aimed to study in vitro toxicological effects of MP on estrogen receptor-negative (ER-ve) MCF-7 breast cancer cell line. Material and Methods: MCF-7 cells were verified immunologically for the presence/absence of ER using immunocytochemistry and flow cytometry. MCF-7 cells were incubated with five MP at serial concentrations of 4×10-5 M, 6×10-5 M, 8×10-5 M, 1×10-4 M and 2×10-4 M. The effect of a single exposure to serial concentrations of MP was studied concerning the proliferation of ER-ve MCF-7 cells. Cell viability was determined using MTT assay. Results: A single exposure to the experimented doses of MP did not demonstrate any stimulatory effect on proliferation of MCF-7 cells with no significant differences between the doses compared to untreated cells. Simultaneously, the applied doses exerted no effect on alpha ER expression. Discussion: In conclusion, a single exposure to MP in various dose ranges did not influence estrogen-ve MCF7 cancer breast cells' growth.
... Although a study has shown that some ingredients, such as parabens, found in cosmetics might make their way into the breasts, the source of parabens was unclear [32]. It was, thus, concluded that these ingredients should not be regarded as the cause of breast cancer [33]. In order to establish clarity on this issue, more epidemiologic studies are needed [34]. ...
Article
Background: This study aimed to explore the effects of cosmetic care on body image (BI), and social avoidance and distress (SAD) in young Chinese breast cancer patients, aged 18–40 years old, receiving adjuvant chemotherapy. Methods: This was a 2-arm quasi-experimental study based on a single-center. A convenience sample of 76 hospitalized young female breast cancer patients, stage 0-III breast cancer diagnosis was recruited. The control group received usual care, while cosmetic care was added to the intervention group. The primary outcomes were BI and SAD accompanying chemotherapy, and the secondary outcome was the appearance satisfaction. It was registered at Clinical Trials.gov, no. NCT04733482. Results: There were significant differences in patients’ body image, and social avoidance and distress scores from the pre-discharge (T0) to at the end of the chemotherapy cycle (T2) between two groups (P < 0.05). However, the intervention did not significantly change the appearance satisfaction at T2 (P > 0.05). Logistic regression suggested there were no confounding demographic factors influencing the intervention. Conclusions: The present study indicated that cosmetic care improved BI and reduced SAD in young Chinese breast cancer patients during adjuvant chemotherapy. However, a randomized study should be undertaken to confirm our results.
... Levels of urinary metabolites of parabens and phthalates have been shown to be higher in Black than White women (22)(23)(24). Parabens and phthalates have also been detected in human breast tumors (25,26). Accumulating evidence from experimental (27)(28)(29)(30) and animal (31,32) studies supports the carcinogenic potential of these chemicals, and increased risk of breast cancer has been associated with exposure to known endocrine disruptors (33) and higher levels of urinary parabens (34) and phthalates (35) in some but not all (36,37) population-based studies. ...
Article
Hair relaxers and leave-in conditioners and oils, commonly used by Black/African American women, may contain estrogens or estrogen-disrupting compounds. Thus, their use may contribute to breast cancer risk. Results of the few previous studies on this topic are inconsistent. We assessed the relation of hair relaxer and leave-in conditioner use to breast cancer incidence in the Black Women's Health Study, a nationwide prospective study of Black women. Among 50,543 women followed from 1997 to 2017, 2,311 incident breast cancers occurred. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression for breast cancer overall and by estrogen receptor (ER) status. For heavy use (≥15 years of use for ≥7 times/ year) of hair relaxers relative to never/light use (<4 years, no more than 1-2 times/year), the multivariable HR for breast cancer overall was 1.13 (95%CI: 0.96-1.33). Duration, frequency, age at first use and number of scalp burns were not associated with overall breast cancer risk. For heavy use of hair relaxers containing lye, the corresponding HR for ER+ breast cancer was 1.32 (95% CI: 0.97, 1.80); there was no association for non-lye products. There was no association of conditioner use and breast cancer. Results of this study were largely null, but there was some evidence that heavy use of lye-containing hair relaxers may be associated with increased risk of ER+ breast cancer. Consistent results from several studies are needed before it can be concluded that use of certain hair relaxers impacts breast cancer development.
... Parabens are widely used as antimicrobial preservatives in personal care products, pharmaceuticals, and food and beverages 42,43 . Parabens can interact with hormone receptors and have been detected in breast tissue 44,45 . Some parabens have demonstrated adverse effects on male reproduction at higher doses 46 . ...
Article
Full-text available
Given the complex exposures from both exogenous and endogenous sources that an individual experiences during life, exposome-wide association studies that interrogate levels of small molecules in biospecimens have been proposed for discovering causes of chronic diseases. We conducted a study to explore associations between environmental chemicals and endogenous molecules using Gaussian graphical models (GGMs) of non-targeted metabolomics data measured in a cohort of California women firefighters and office workers. GGMs revealed many exposure-metabolite associations, including that exposures to mono-hydroxyisononyl phthalate, ethyl paraben and 4-ethylbenzoic acid were associated with metabolites involved in steroid hormone biosynthesis, and perfluoroalkyl substances were linked to bile acids—hormones that regulate cholesterol and glucose metabolism—and inflammatory signaling molecules. Some hypotheses generated from these findings were confirmed by analysis of data from the National Health and Nutrition Examination Survey. Taken together, our findings demonstrate a novel approach to discovering associations between chemical exposures and biological processes of potential relevance for disease causation.
... It notes that humans are directly exposed to parabens during the usage of PPCPs. Hence, parabens could be found in the human body, such as human tissue (up to 5,103 mg g À1 (Barr et al., 2012)) and urine samples (up to 1,710 mg L À1 (Hines et al., 2015)), etc. However, based on currently available scientific information, it is premature to claim that parabens are safe for use or involved in the genesis or propagation of these controversial and important health problems (Fransway et al., 2019). ...
Article
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.
... Some studies have related the use of parabens in cosmetics with the presence of these compounds in breast tumor, which may not determine the cause of the disease but may be pre-conditions in its advance (Darbre et al., 2004;Witorsch & Thomas, 2010;Barr et al., 2012;Hu et al., 2012;Dubey et al., 2017). Darbre et al. (2004), quantified methylparaben in 62% of tumors, at the mean concentration of 100 ng/g tissue. ...
Article
Full-text available
Objective: To summarize evidence regarding the toxic potential of administering parabens-containing cosmetics in humans. Methods: The systematic review followed the methodology proposed in Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). Electronic searches of the PubMed, Virtual Health Library (BVS), and Science Direct databases were performed between October 1 st and 31 st , 2018. No language restriction was determined. Original articles reporting observational, in vitro and in silico studies of toxicity caused by parabens in human or human cells were considered for eligibility. Two independent reviewers performed data extraction and assessed the methodological quality and risk of bias of articles by using the Downs & Black Scale. Score levels greater than 70% were assumed to reflect good methodological quality. The Kappa coefficient was calculated. Results: A total of 254 studies were found. Following the eligibility evaluation, 22 studies were included for the qualitative synthesis. The concordance between the reviewers was substantial (Kappa coefficient = 0.650). The meaningful reported outcomes were: high concentrations of parabens in the body; apoptosis damage to sperm DNA; oxidative stress; DNA damage; irritative potential; interference in the control of adipogenesis; estrogenic activity; genotoxicity; necrosis; role in carcinogenesis of breast cancer; harmful effects on human skin when exposed to the sun; stimulation of oncogenes expression; and interference with DNA transcription. Despite most included articles presenting appreciable methodological quality, remarkable limitations were observed and the mechanisms by which parabens exert toxicity on humans remained unclear. Conclusions: The accumulation of parabens in the human organism following repeated cosmetics administration on the skin is noteworthy. However overall, the evidence so far does not make it possible to determine whether, and in what extent, the use of paraben-containing cosmetics can disturb human health. Further investigations are still required for clarifying these issues.
... The established concentrations of parabens which cause the maximum growth of human breast cancer cells in vitro have been compared to the measured paraben concentrations in breast tissue (Charles and Darbre, 2013) and it has been demonstrated that single parabens or their combinations can increase proliferation of human breast cancer cells at the concentrations detected in breast cancer tissue. Parabens were first detected in human breast tumor tissue in 2004 (Darbre et al., 2004) and were later confirmed to be ubiquitous in all regions of the human breast at the median concentrations of 168 ng/g for PrP, 16.6 ng/g for MeP, and 85.5 ng/g for total parabens (Barr et al., 2012). These results highlight the importance of monitoring paraben exposure concentrations in humans. ...
Article
Parabens are one of the most widely used preservatives in food, pharmaceuticals and personal care products (PCPs) because of their advantageous properties and low toxicity based on the early assessments. However, recent research indicates that parabens may act as endocrine-disrupting chemicals (EDCs) and thus, are considered as chemicals of emerging concern that have adverse human health effects. To provide the basis for future human health studies, we reviewed relevant literature, published between 2005-2020, regarding the levels of parabens in the consumer products (pharmaceuticals, PCPs and food), environmental matrices and humans, including susceptible populations, such as pregnant women and children. The analysis showed that paraben detection rates in consumer products, environmental compartments and human populations are high, while the levels vary greatly by country and paraben type. The concentrations of parabens reported in pregnant women (~20-120 μg/L) were an order of magnitude higher than in the general population. Paraben concentrations in food and pharmaceuticals were at the ng/g level, while the levels in PCPs reached mg/g levels. Environmental concentrations ranged from ng/L - μg/L in surface waters to tens of μg/g in wastewater and indoor dust. The levels of human exposure to parabens appear to be higher in the U.S. and EU countries than in China and India, which may change with the increasing production of parabens in the latter countries. The review provides context for future studies to connect paraben exposure levels with human health effects.
... paraben esters have been reported to be detected in breast tissue biopsies, and antiperspirants have been suggested to be the source (Darbre et al. 2004). However, the risk assessment for humans has become highly challenging, as inconclusive or contradictory results have been demonstrated by numerous studies in vivo and in vitro or in combined test batteries (e.g., Tayama et al. 2008, Roszak et al. 2017, Barr et al. 2012, Fransway et al. 2019, Soni et al. 2005, Kang et al. 2013b, Darbre and Harvey 2008, Kim et al. 2020, Bilal and Iqbal 2019. Official scientific opinions summarize in their studies that the use of parabens is safe for human health as parabens are metabolised to benzoic acid in the human body and excreted in the urine, with benzoic acid being practically free of toxic effects in numerous tests and unlikely to interfere with chromosomes (SCF 1994, SCCP 2011, SCCP 2013. ...
Article
Growing worldwide efforts to replace (reduce) animal testing and to improve alternative in vitro tests which may be more efficient in terms of both time, cost and scientific validity include also genotoxicity/mutagenicity endpoints. The aim of the review article was to summarize currently available in vitro testing approaches in this field, their regulatory acceptance and recommended combinations for classification of chemicals. A study using the combination of Comet Assay performed on two cell lines and the Chromosomal Aberration test on human peripheral lymphocytes was performed with the aim to predict the genotoxic potential of selected paraben esters, serving as a model chemical group. Parabens are widely used in consumer products as preservatives and have been reported to exhibit inconclusive results in numerous genotoxicity studies. The Comet Assay identified Ethylparaben and Benzylparaben as potentially genotoxic. The Chromosomal Aberration test revealed weak genotoxic potential in case of Ethylparaben and positive genotoxicity in case of Butylparaben, Propylparaben and Isopropylparaben. The main reasons for variability seem to be limited water solubility of parabens, determining their bioavailability at the cellular level, and absence of metabolic activation in the Comet Assay. The results confirmed that the Comet Assay should serve as a screening test and should not be used as a stand-alone method for classification of genotoxicity. The weight of evidence approach in risk assessment should be supported with data generated with the use of human relevant in vitro methods based on cells / tissues of human origin.
... The earliest studies that raised public attention about parabens examined paraben concentrations in cosmetics, including underarm deodorants, and the risk of breast cancer [2, 3, 4••]. Since those early studies, additional evaluations have documented parabens in breast adipose tissue, with the highest concentrations reported for PP (median concentrations = 16.8 ng/g adipose) [88]. In surveys across different zones of the breast, PP was measured at the highest concentrations near the axilla, which the authors conclude is consistent with an underarm cosmetic source [89]. ...
Article
Full-text available
Purpose Parabens are chemicals containing alkyl-esters of p-hydroxybenzoic acid, which give them antimicrobial, antifungal, and preservative properties. Propylparaben (PP) is one paraben that has been widely used in personal care products, cosmetics, pharmaceuticals, and food. In this review, we address the ongoing controversy over the safety of parabens, and PP specifically. These chemicals have received significant public attention after studies published almost 20 years ago suggested plausible associations between PP exposures and breast cancer. Recent Findings Here, we use key characteristics, a systematic approach to evaluate the endocrine disrupting properties of PP based on features of “known” endocrine disruptors, and consider whether its classification as a “weak” estrogen should alleviate public health concerns over human exposures. We also review the available evidence from rodent and human studies to illustrate how the large data gaps that exist in hazard assessments raise concerns about current evaluations by regulatory agencies that PP use is safe. Finally, we address the circular logic that is used to suggest that because PP has been used for several decades, it must be safe. Summary We conclude that inadequate evidence has been provided for the safe use of PP in food, cosmetics, and consumer products.
... 57 Many studies have proved the role of parabens, used as preservatives in cosmetics, in breast cancer. [58][59][60] Exposure to hair dyes increases the chances of leukemia, non-Hodgkin's lymphomas, and bladder cancer. [60][61][62][63] In another study, it has been reported that personal use of darker hair dyes and relaxants are involved in estrogen receptor-positive and estrogen-receptor breast cancer. ...
Article
Full-text available
To look superior and acceptable in society, people from all over the world use various types of cosmetic products to enhance or alter their facial appearance and body texture. In recent times, an exponential surge in cosmetic use has been observed in Pakistan, and hence spending money on personal-care products is high. However, there are many reported facts about high loads of lead, mercury, copper, and others hazardous and cancerous elements in local Pakistani cosmetic brands. Consumers of these brands are at high risk of many clinical issues, including cancer. As such, it is a necessity to make people aware of the devastating harmful effects related to cosmetic use. The aim of this study was to provide information for stakeholders and raise awareness in the general public about the use of these local unauthorized personal-care cosmetic products, along with government strategies to stop this cosmetic blight on human health.
... Personal care products are produced in huge quantities due to their everyday usage so any preservatives used in these products must be completely safe for human use (Błedzka, Gromadzinska, and Wasowicz 2014). PBs were detected in human breast tissue, with a mean paraben level of 20 ng g À1 (Darbre et al. 2004), paraben-derived oestradiol equivalents of 1.28 nmol/L (Harvey and Everett 2006), as well as median value for total paraben mixture of 85.5 ng g À1 (Barr et al. 2012). In addition to this, ethyl and n-propyl parabens, at the highest median concentrations (43.9 ng/mL and 9.05 ng/mL, respectively), were found in urine samples (Ye et al. 2006), while methylparaben median value of 9.4 ng/mL, ethylparaben median <3 ng/mL and propylparaben median <2 ng/mL have been reported in plasma samples (Sandanger et al. 2011). ...
Article
The aim of this study was to determine the cytogenotoxic effects of methylparaben, ethylparaben and butylparaben using battery of tests in plant cells (Allium cepa assay) and human lymphocytes (chromosome aberration test and alkaline comet assay). Our results for A. cepa assay showed that none of the tested parabens showed an inducing effect on root growth. Mitotic index values decreased with increasing parabens concentration. Ethylparaben (0.10 mg/L) induced a higher number of vagrants and multipolarity, as well as the number of sticky chromosomes (0.50 mg/L), while butylparaben (0.25 and 0.50 mg/L) increased the frequency of sticky chromosomes. Higher frequency of apoptosis and necrosis was observed for ethylparaben (0.50 mg/L) and methylparaben (0.10 and 0.50 mg/L). As for chromosome aberrations test in human lymphocytes, the mitotic index was reduced with an increase in the concentration of all three tested parabens. Differences between methylparaben (0.25 mg/L), ethylparaben (0.10 mg/L) and butylparaben (0.25 mg/L) and controls for acentric fragments, chromatid breaks and polyploidy were observed. Increased frequency of apoptosis was induced by methylparaben and ethylparaben at concentrations of 0.25 and 0.50 mg/L. Alkaline comet assay demonstrated that 0.25 and 0.50 mg/L of ethylparaben and butylparaben have genotoxic potential by increasing the tail intensity against controls. These results suggest that methyl-, ethyl- and butylparaben possess certain geno/cytotoxic potential.
... Later, a Norwegian study reported that paraben esters can be measured in over 60% of blood samples taken from the general population and that there was a significant association between blood paraben concentration and selfreported use of personal care products. 62 Human serum albumin (HSA) is the most abundant protein in blood plasma (up to 40mg/ml; 0.6mM) and accounts for about 60% of the plasma's total protein content. It can bind reversibly to a wide variety of endogenous and exogenous substances and so may play an important role in the transport and deposition of these substances. ...
Thesis
Full-text available
Preservatives are common ingredients widely used in everyday products. Parabens are the most commonly used preservative in cosmetics and topical medications. The safety of parabens for use as a preservative in cosmetics has come into question; and thus consumer demand for paraben-free products is ever increasing. In this study Shimadzu Reversed phase High Performance Liquid Chromatography method developed for the separation of two paraben preservatives (methyl- and propyl parabens) using a Luna C18(2) column (5u, 250 mm x 4.6 mm) in 10 marketed cosmetics products. The separation was completed within 21 min where Methyl and Propyl Paraben Retention Time was around 14.6931 minutes and 20.4422 minutes respectively at a flow rate of 1 ml/min and a binary gradient mobile phase containing water and acetonitrile have been used in different proportions. The method was applied and validated satisfactorily for the determination of these parabens in commercial cosmetics samples. The levels of the two parabens determined in 8 cosmetic product samples were not in agreement with the European Union Cosmetic Directive (EU Cosmetics Directive 76/768/EEC).
... Later, a Norwegian study reported that paraben esters can be measured in over 60% of blood samples taken from the general population and that there was a significant association between blood paraben concentration and selfreported use of personal care products. 62 Human serum albumin (HSA) is the most abundant protein in blood plasma (up to 40mg/ml; 0.6mM) and accounts for about 60% of the plasma's total protein content. It can bind reversibly to a wide variety of endogenous and exogenous substances and so may play an important role in the transport and deposition of these substances. ...
Thesis
Full-text available
Abstract Preservatives are common ingredients widely used in everyday products. Parabens are the most commonly used preservative in cosmetics and topical medications. The safety of parabens for use as a preservative in cosmetics has come into question; and thus consumer demand for paraben-free products is ever increasing. In this study Shimadzu Reversed phase High Performance Liquid Chromatography method developed for the separation of two paraben preservatives (methyl- and propyl parabens) using a Luna C18(2) column (5u, 250 mm x 4.6 mm) in 10 marketed cosmetics products. The separation was completed within 21 min where Methyl and Propyl Paraben Retention Time was around 14.6931 minutes and 20.4422 minutes respectively at a flow rate of 1 ml/min and a binary gradient mobile phase containing water and acetonitrile have been used in different proportions. The method was applied and validated satisfactorily for the determination of these parabens in commercial cosmetics samples. The levels of the two parabens determined in 8 cosmetic product samples were not in agreement with the European Union Cosmetic Directive (EU Cosmetics Directive 76/768/EEC).
... Later, a Norwegian study reported that paraben esters can be measured in over 60% of blood samples taken from the general population and that there was a significant association between blood paraben concentration and selfreported use of personal care products. 62 Human serum albumin (HSA) is the most abundant protein in blood plasma (up to 40mg/ml; 0.6mM) and accounts for about 60% of the plasma's total protein content. It can bind reversibly to a wide variety of endogenous and exogenous substances and so may play an important role in the transport and deposition of these substances. ...
Book
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
Article
Parabens are a group of alkyl esters of p‐hydroxybenzoic acid added to consumer products to prevent the growth of harmful bacteria and molds. Parabens are hypothesized to increase the risk of breast cancer (BC); however, no study has examined the interactions between parabens, global DNA methylation (DNAm), and BC risk. We examined the modifying effects of DNAm on the associations between parabens and BC, and whether parabens were associated with BC defined by tumor promoter methylation status. Participants included 708 cases and 598 controls from the Long Island Breast Cancer Study Project. Methylparaben (MPB), propylparaben, and butylparaben levels were measured in spot urine samples. Global DNAm was measured by analysis of long interspersed elementes‐1 (LINE‐1) and the luminometric methylation assay (LUMA). The promoter methylation status of 13 genes was measured in tumor samples from 509 cases. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between parabens and BC stratified by LINE‐1/LUMA, and between parabens and gene‐specific promoter methylation‐defined BC. Outcome heterogeneity was evaluated using ratios of ORs (RORs). We assessed the joint effects of the multiple parabens using quantile g‐computation. The highest versus lowest tertile of MPB and a one‐quantile increase in all parabens were associated with ORs of 1.46 (95% CI = 0.96–2.23) and 1.32 (95% CI = 1.02–1.71), respectively, among women with hypomethylated LINE‐1. A one‐ln unit increase in MPB was associated with a 25% increase in the odds of hypomethylated (vs. hypermethylated) CCND2 promoter‐defined BC (ROR = 1.25, 95% CI = 1.06–1.48), and a one‐quantile increase in all parabens was associated with a 55% increase in the odds of hypomethylated (vs. hypermethylated) CCND2 promoter‐defined BC (ROR = 1.55, 95% CI = 1.04–2.32). Exposure to parabens may increase the risk of BC among women with hypomethylated global DNAm and may increase the risk of tumors with gene‐specific hypomethylated promoter regions.
Article
Cosmetics, cosmeceuticals, and variable healthcare products used parabens, among other excipients, for their preservative and antimicrobial activities. Paraben derivatives exhibit distinguished physiochemical properties that enable them to be compatible with the formulation of cosmetic agents in different dosage forms. In addition to their potency and efficacy, parabens are economically efficient as they have low-manufacturing costs. Despite the desirable characteristics, the safety of parabens use is controversial after detecting these chemicals in various biological tissues after repetitive and long-term use of formulations containing them. The use of parabens drew public health attention after scientific reports linked skin exposure to parabens with health issues, in particular, breast cancer. In response, worldwide authorities set regulations for the allowance concentrations of paraben to be used in variable cosmetic products.
Article
Cosmetics, cosmeceuticals, and variable healthcare products used parabens, among other excipients, for their preservative and antimicrobial activities. Paraben derivatives exhibit distinguished physiochemical properties that enable them to be compatible with the formulation of cosmetic agents in different dosage forms. In addition to their potency and efficacy, parabens are economically efficient as they have low manufacturing costs. Despite the desirable characteristics, the safety of parabens use is controversial after detecting these chemicals in various biological tissues after repetitive and long-term use of formulations containing them. The use of parabens drew public health attention after scientific reports linked skin exposure to parabens with health issues, in particular, breast cancer. In response, worldwide authorities set regulations for the allowance concentrations of paraben to be used in variable cosmetic products.
Chapter
This chapter begins with an overview of the extent to which endocrine-disrupting chemicals (EDCs) can enter human tissues from environmental exposure. Retention of EDCs in body tissues may be influenced both by their route of entry and by their resistance to physiological clearance processes. Their endocrine-disrupting activity and biological availability may also be influenced by endogenous metabolic reactions. Measurements using a range of body tissues have demonstrated the ubiquitous distribution of many EDCs across the human population, but the source of the body burden is difficult to establish due to the widespread use of these compounds. The measurement of so many different EDCs in human tissues demonstrates the potential for mixtures of EDCs at low doses to interfere in the long term on hormone regulation with adverse consequences for human health. Many different nonlinear, nonmonotonic dose responses to EDCs have been demonstrated, and effects at high doses may not always be predictive of effects at low doses. The effects of EDCs vary in different tissues and between individuals, but timing is also important. Critical windows of susceptibility to EDC exposure exist during prenatal life and early childhood, and some exposures to EDCs in utero can produce long-lasting effects into adult life and onto future generations.
Chapter
This chapter outlines some of the principles on which regulation of endocrine disrupting chemicals (EDCs) depends, and provides an introduction to the concepts of hazard, weight of evidence, and risk. Challenges for the regulation of chemicals which act through endocrine mechanisms are discussed. The value and limitations of different types of evidence for the assessment process and the approach of constructing adverse outcome pathways to identify key events and representative endpoints are described. Contributions to the regulatory processes by government, regulatory bodies (national and international), nongovernment organizations, the media, citizen responsibility, and the precautionary principle are outlined.
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This chapter provides an overview of the chemical components of personal care products (PCPs) that possess endocrine-disrupting activity and cites evidence that such endocrine-disrupting chemicals (EDCs) can be absorbed from application to human skin. Reported cases are described where absorption of EDCs from PCPs has affected human endocrine health. The use of PCPs presents high dermal exposure to multiple EDCs on a daily basis, and many of these EDCs have been measured in human tissue. Although it is not possible to identify the source of each EDC measured in human tissue, many of these chemicals are used only in PCPs, and several studies have found an association between concentrations measured in the tissue and self-reported use of PCPs. Dermal application of PCPs as a source of EDCs is an emerging issue, and national and international regulatory bodies are moving toward greater regulation of the component chemicals.
Chapter
This chapter discusses the potential for endocrine-disrupting chemicals (EDCs) to influence the development of cancer in female endocrine-sensitive tissues of the breast, endometrium, ovary, and cervix, and in male hormone-regulated tissues of the prostate, testis, and breast. Hanahan and Weinberg have established a framework for understanding the complexity of cancer development through their definition of hallmarks and enabling characteristics, and this offers the opportunity to explore the ability of complex environmental mixtures of EDCs to affect cancer. It is not necessary for each EDC to affect all the hallmarks, but if a mixture of EDCs can together affect all the hallmarks, and do so at environmentally relevant concentrations measurable in human tissues, then there is the potential for cancer development.
Chapter
The human population is exposed to endocrine-disrupting chemicals (EDCs) as complex mixtures through inhalation (air), oral intake (water, food), or dermal applications (household and personal care products), and the measurement of so many hundreds of EDCs in human body tissues implies that adverse effects on human endocrine health must also be considered as resulting from exposure not to single chemicals but to complex mixtures in the target tissues. Much of the scientific evidence for endocrine disruption comes from studies of single chemicals, but this chapter will review emerging evidence that chemical mixtures can cause endocrine disruption through additive mechanisms between EDCs with a similar mode of action, and complementary mechanisms between EDCs with different modes of action. Since EDCs are present in human body tissues over the long term, often building up over many years, the effects of exposure to EDCs over long periods of time rather than just a short time frame is a relevant environmental issue. Most in vitro assays are performed over a period of hours or days, and emerging evidence is discussed that consequences may arise in cells after long-term EDC exposures which are not observed following only short-term exposures.
Article
Introduction: Parabens are a group of chemicals widely used as preservatives in daily consumer products such as cosmetics, food items, pharmaceuticals and household commodities. They have been broadly detected in human samples indicating a general human exposure, and concerns arose from their potential endocrine disrupting effect. Especially the exposure to parabens during pregnancy is concerning, as the time of fetal development is a particularly vulnerable period. The aim of this study was to investigate the transport and metabolism of four commonly used parabens: methyl-, ethyl-, propyl- and butylparaben (MeP, EtP, PrP and BuP) and the metabolite para-hydroxybenzoic acid (PHBA) across the human placenta. Methods: An ex-vivo human placental perfusion model was used. The test compounds were added in the maternal compartment (with initial concentrations of 1 mM or 0.1 mM). Placental transport was evaluated by fetal-maternal concentration ratios (FM-ratio), transport index (TI) and indicative permeability (IP). Results: Information about parabens kinetics was taken from 10 perfusions and PHBA from 7 perfusions. Paraben metabolism was not detected. The placental transport of MeP, EtP, PrP, BuP and PHBA revealed a transfer from maternal to fetal circulations with FM120 of 0.86 ± 0.27 (MeP), 0.98 ± 0.28 (EtP), 1.00 ± 0.28 (PrP), 1.12 ± 0.59 (BuP) and 0.82 ± 0.37 (PHBA). The test substances accumulated in the perfused tissue in some degree. The average kinetic parameters FM-ratio, TI and IP were not different between chemicals. Discussion: The present study shows that the placenta barrier is permeable to all four parabens and the metabolite, which implies potential fetal exposure.
Chapter
Many hundreds of endocrine disrupting chemicals (EDCs) have been measured as entering human breast tissue from a range of environmental sources, and this review focuses on discussion of mechanisms by which such EDCs may be contributing to the globally rising incidence of breast cancer. Many of the distinguishing features of breast cancer may be accounted for by EDC exposure, including, but not limited to, the fact that many EDCs possess estrogenic activity and exposure to estrogen is a main risk factor for breast cancer. Studies of the actions of EDCs in human breast cancer cells are aided by use of the conceptual framework of the hallmarks of cancer, and, acting by a variety of genomic and nongenomic mechanisms, EDCs have now been shown to enable all the hallmarks of cancer to develop in human breast cancer cells. Many studies report that hallmarks can develop at concentrations which are within the range of those measured in human breast tissues, especially when added as mixtures. The varied levels of different EDCs measured in individual breast tissue samples together with the overlapping and complementary mechanisms of action of the EDCs imply that thematic mechanisms will be driven inevitably by different chemical mixtures. Despite the complexity, EDCs do need to now be acknowledged as a risk factor for breast cancer in order for preventative strategies to include reduction in EDC exposure.
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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
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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.
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Chloride ion (Cl⁻) widely presents in natural water and wastewater, which can significantly affect the performance of sulfate radical-based advanced oxidation processes (SR-AOPs). However, few studies are available now on the generation of chlorinated by-products in the peroxymonosulfate (PMS) based systems. Here a novel catalyst (cobalt/carbon nanotubes, Co/CNTs) was synthesized and used as a PMS activator to remove methylparaben (MeP) with and without Cl⁻. The morphology and chemical composition of the fresh and used Co/CNTs were characterized by TEM, SEM, XRD, BET, and XPS. Results revealed that Co/CNTs exhibited significant catalytic activity toward MeP removal, and the removal efficiency increased with the augment of reaction temperature and concentrations of Co/CNTs and PMS. In the absence of Cl⁻, 83.2% of 10 μM MeP was degraded within 60 min by using 2 mg/L Co/CNTs and 100 μM PMS at 25 °C with pH 7.0. However, complete removal of MeP was achieved within 20 min in the presence of 100 mM Cl⁻, which enhanced the apparent rate constant by a factor of 4.3. Consequently, TOC removal was enhanced from 8.1% to 19.2% within 60 min. Through the quenching experiments, both SO4⁻ and OH were found responsible for MeP degradation without Cl⁻, while Cl2⁻ was the main reactive oxygen species (ROS) with 100 mM Cl⁻. Based on the intermediates identified via TOF-LC-MS, four potential reaction pathways were proposed, including hydrogen abstraction coupling reaction, hydroxylation, OH attack, and Cl2⁻ attack. The intermediates also exhibited decreased toxicity compared to the parent compound based on the ecotoxicity evaluation. In addition, Co/CNTs + PMS system achieved over 60% MeP removal from real wastewater with elevated PMS concentration, indicating the process applicability. These findings provide valuable information of SR-AOPs to facilitate organic contaminants removal in Cl⁻-containing water.
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Existing studies monitoring organochlorine pesticide residues in breastmilk were examined to identify whether common factors determine the extent of transfer of these residues. A structured review of the English language literature was conducted. Papers were reviewed and assessed using a structured protocol. A total of 77 papers were initially identified, 46 of which contained conclusions relating to the factors which may affect the transfer of residues into breastmilk. Owing to the diversity of findings, papers were screened further to include only those in which a minimum of background information relating to selection of mothers and to milk sampling procedures were reported. Only eight papers were deemed to contain adequate information. Age, parity/length of previous lactation, fat mobilisation and the time of sampling were identified as the most likely factors to be considered when assessing transfer of organochlorine pesticide residues into breastmilk. This review highlights the difficulties of assessing trends in breastmilk contaminants where comparable sampling procedures are not used.
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Parabens are used extensively in personal care products; however, their estrogenic properties have raised concern over risks to human health. High levels of total parabens, mainly as conjugates, have been reported in human plasma/serum, with limited data on native parabens. Our objective was to assess and link plasma concentrations of native common parabens to self-reported use of personal care products in women from the general population. The information was obtained from an extensive questionnaire on diet and lifestyle previously answered by the women in the NOWAC study. Plasma samples from 332 individuals were extracted and cleaned up by automated solid phase extraction and analyzed by ultra high performance liquid chromatography time-of-flight mass spectrometry. Native methyl paraben dominated and was detected in 63% of the samples, with a median level of 9.4 ng/ml. Ethyl paraben (median < 3 ng/ml) and propyl paraben (median < 2 ng/ml) were detected in 22 and 29%, respectively. Butyl and benzyl parabens were not detected. For the first time, elevated levels of native parabens are reported in women from the general population. The concentrations were significantly associated with the use of skin lotions, indicating that frequent (daily or more) use maintain elevated concentrations despite the parabens short half-lives. These findings clearly emphasize the need to study potential health effects in the general population.
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Parabens are commonly used as antimicrobial preservatives in cosmetics, pharmaceuticals, and food and beverage processing. Widespread human exposure to parabens has been recently documented, and some parabens have demonstrated adverse effects on male reproduction in animal studies. However, human epidemiologic studies are lacking. We investigated relationships between urinary concentrations of parabens and markers of male reproductive health in an ongoing reproductive epidemiology study. Urine samples collected from male partners attending an infertility clinic were analyzed for methyl paraben (MP), propyl paraben (PP), butyl paraben (BP), and bisphenol A (BPA). Associations with serum hormone levels (n = 167), semen quality parameters (n = 190), and sperm DNA damage measures (n = 132) were assessed using multivariable linear regression. Detection rates in urine were 100% for MP, 92% for PP, and 32% for BP. We observed no statistically significant associations between MP or PP and the outcome measures. Categories of urinary BP concentration were not associated with hormone levels or conventional semen quality parameters, but they were positively associated with sperm DNA damage (p for trend = 0.03). When urinary BPA quartiles were added to the model, BP and BPA were both positively associated with sperm DNA damage (p for trend = 0.03). Assessment of paraben concentrations measured on repeated urine samples from a subset of the men (n = 78) revealed substantial temporal variability. We found no evidence for a relationship between urinary parabens and hormone levels or semen quality, although intraindividual variability in exposure and a modest sample size could have limited our ability to detect subtle relationships. Our observation of a relationship between BP and sperm DNA damage warrants further investigation.
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Parabens are widely used as antimicrobial preservatives in cosmetics, -pharmaceuticals, and food and beverage processing. We assessed exposure to methyl, ethyl, propyl, and butyl parabens in a representative sample of persons >or= 6 years of age in the U.S. general population from the 2005-2006 National Health and Nutrition Examination Survey. We analyzed 2,548 urine samples by using online solid-phase extraction coupled to isotope dilution-high-performance liquid chromatography/tandem mass spectrometry. We detected methyl paraben (MP) and propyl paraben (PP) in 99.1% and 92.7% of the samples, respectively. We detected ethyl (42.4%) and butyl (47%) parabens less frequently and at median concentrations at least one order of magnitude lower than MP (63.5 microg/L) and PP (8.7 microg/L). Least-square geometric mean (LSGM) concentrations of MP were significantly higher (p <or= 0.01) among non-Hispanic blacks than among non-Hispanic whites except at older ages (>or= 60 years). Adolescent and adult females had significantly higher (p < 0.01) LSGM concentrations of MP and PP than did adolescent and adult males. Females were more likely than males [adjusted odds ratios (ORs) and 95% confidence intervals (CIs): MP, 3.2 (2.99-5.27); PP, 4.19 (2.34-7.49)] and non-Hispanic blacks were more likely than non-Hispanic whites [MP, 4.99 (2.62-9.50); PP, 3.6 (1.86-7.05)] to have concentrations above the 95th percentile. The general U.S. population was exposed to several parabens during 2005-2006. Differences in the urinary concentrations of MP and PP by sex and race/ethnicity likely reflect the use of personal care products containing these compounds.
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Conventional wisdom regarding exposures to persistent organic chemicals via breast-feeding assumes that concentrations decline over the course of lactation and that the mother's body burden reflects her cumulative lifetime exposure. Two important implications stemming from these lines of thought are, first, that assessments of early childhood exposures should incorporate decreasing breast milk concentrations over lactation; and, second, that there is little a breast-feeding mother can do to reduce her infant's exposures via breast-feeding because of the cumulative nature of these chemicals. We examined rates of elimination and milk/serum partition coefficients for several groups of persistent organic chemicals. We collected simultaneous milk and blood samples of 10 women at two times postpartum and additional milk samples without matching blood samples. Contrary to earlier research, we found that lipid-adjusted concentrations of polybrominated diphenyl ethers, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins and furans, and organochlorine pesticides in serum and milk do not consistently decrease during lactation and can increase for some women. Published research has also suggested an approximate 1:1 milk/serum relationship (lipid adjusted) on a population basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin; however, our results suggest a more complex relationship for persistent, lipophilic chemicals with the milk/serum relationship dependent on chemical class. Decreases in concentration of lipophilic chemicals on a lipid-adjusted basis during lactation should no longer be assumed. Thus, the concept of pumping and discarding early milk as means of reducing infant exposure is not supported. The hypothesis that persistent lipophilic chemicals, on a lipid-adjusted basis, have consistent concentrations across matrices is likely too simplistic.
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Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. We conducted a PubMed search in October 2008 and retrieved 494 studies. Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.
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Research on environmentally related chemical contaminants in breast milk spans several decades and dozens of countries. The ability to use this research as an environmental indicator is limited because of a lack of consistent protocols. Data on xenobiotics in breast milk are influenced by choices in sample selection, sample pooling, analysis, and reporting. In addition, most studies have focused only on a small panel of persistent organic pollutants, despite indications that a wide range of additional chemical contaminants may also enter breast milk. Despite these limitations, however, it is possible to draw some generalizations. In this paper we review available data on levels of organochlorine pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs), polybrominated diphenyl ethers (PBDEs), metals, and solvents in breast milk. Examples drawn from around the world illustrate the available data and the patterns that have appeared in various areas over time. Over the past few decades, levels of the organochlorine pesticides, PCBs, and dioxins have declined in breast milk in countries where these chemicals have been banned or otherwise regulated. In contrast, the levels of PBDEs are rising. Regional differences in levels of xenobiotics in breast milk are related to historical and current local use patterns. Diet is a major factor that influences breast milk levels of persistent organic pollutants, with patterns in fish consumption playing a particularly significant role. Improved global breast milk monitoring programs would allow for more consistent data on trends over time, detection of new xenobiotics in breast milk, and identification of disproportionately exposed populations.
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Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term, low-dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin-layer chromatography. More detailed studies enabled identification and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 +/- 4.2 ng x g(-1) tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 +/- 2.2 ng x g(-1) tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues.
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Human milk is the best natural and optimal food for neonates with several immunologic, developmental and practical advantages throughout childhood. Although the World Health Organization strongly supports breastfeeding, it recognizes the potential health risks posed by the presence of environmental toxicants in breast milk. Contamination of human milk is widespread and due to decades of inadequately controlled pollution by toxicants, persistent pesticides or chemical solvents. These chemicals tend to degrade slowly in the environment, to bioaccumulate in the food chain and to have long half-lives in humans. Many of these environmental pollutants have estrogen-like activities and, thus they are called environmental estrogen disruptors or xenoestrogens. Certain adverse health and reproductive outcomes are attributed to these chemicals in laboratory animals and in wildlife as well as in humans. Here, we review available data from breast milk monitoring studies suggesting the environmental chemicals that may affect child health through breastfeeding.
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Parabens are a group of the alkyl esters of p-hydroxybenzoic acid and typically include methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, isopropylparaben, and benzylparaben. Parabens (or their salts) are widely used as preservatives in cosmetics, toiletries, and pharmaceuticals due to their relatively low toxicity profile and a long history of safe use. Testing of parabens has revealed to varying degrees that individual paraben compounds have weakly estrogenic activity in some in vitro screening tests, such as ligand binding to the estrogen receptor, regulation of CAT gene expression, and proliferation of MCF-7 cells. Reported in vivo effects include increased uterine weight (i.e., butyl-, isobutyl-, and benzylparaben) and male reproductive-tract effects (i.e., butyl- and propylparaben). However, in relation to estrogen as a control during in vivo studies, the parabens with activity are many orders of magnitude less active than estrogen. While exposure to sufficient doses of exogenous estrogen can increase the risk of certain adverse effects, the presumption that similar risks might also result from exposure to endocrine-active chemicals (EACs) with far weaker activity is still speculative. In assessing the likelihood that exposure to weakly active EACs might be etiologically associated with adverse effects due to an endocrine-mediated mode of action, it is paramount to consider both the doses and the potency of such compounds in comparison with estrogen. In this review, a comparative approach involving both dose and potency is used to assess whether in utero or adult exposure to parabens might be associated with adverse effects mediated via an estrogen-modulating mode of action. In utilizing this approach, the paraben doses required to produce estrogenic effects in vivo are compared with the doses of either 17beta-estradiol or diethylstilbestrol (DES) that are well established in their ability to affect endocrine activity. Where possible and appropriate, emphasis is placed on direct comparisons with human data with either 17beta-estradiol or DES, since this does not require extrapolation from animal data with the uncertainties inherent in such comparisons. Based on these comparisons using worst-case assumptions pertaining to total daily exposures to parabens and dose/potency comparisons with both human and animal no-observed-effect levels (NOELs) and lowest-observed-effect levels (LOELs) for estrogen or DES, it is biologically implausible that parabens could increase the risk of any estrogen-mediated endpoint, including effects on the male reproductive tract or breast cancer. Additional analysis based on the concept of a hygiene-based margin of safety (HBMOS), a comparative approach for assessing the estrogen activities of weakly active EACs, demonstrates that worst-case daily exposure to parabens would present substantially less risk relative to exposure to naturally occurring EACs in the diet such as the phytoestrogen daidzein.
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Parabens appear frequently as antimicrobial preservatives in cosmetic products, in pharmaceuticals, and in food and beverage processing. In vivo and in vitro studies have revealed weak estrogenic activity of some parabens. Widespread use has raised concerns about the potential human health risks associated with paraben exposure. Assessing human exposure to parabens usually involves measuring in urine the conjugated or free species of parabens or their metabolites. In animals, parabens are mostly hydrolyzed to p-hydroxybenzoic acid and excreted in the urine as conjugates. Still, monitoring urinary concentrations of p-hydroxybenzoic acid is not necessarily the best way to assess exposure to parabens. p-hydroxybenzoic acid is a nonspecific biomarker, and the varying estrogenic bioactivities of parabens require specific biomarkers. Therefore, we evaluated the use of free and conjugated parent parabens as new biomarkers for human exposure to these compounds. We measured the urinary concentrations of methyl, ethyl, n-propyl, butyl (n- and iso-), and benzyl parabens in a demographically diverse group of 100 anonymous adults. We detected methyl and n-propyl parabens at the highest median concentrations (43.9 ng/mL and 9.05 ng/mL, respectively) in nearly all (> 96%) of the samples. We also detected other parabens in more than half of the samples (ethyl, 58%; butyl, 69%). Most important, however, we found that parabens in urine appear predominantly in their conjugated forms. The results, demonstrating the presence of urinary conjugates of parabens in humans, suggest that such conjugated parabens could be used as exposure biomarkers. Additionally, the fact that conjugates appear to be the main urinary products of parabens may be important for risk assessment.
Article
Parabens is the name given to a group of p-hydroxybenzoic acid (PHBA) esters used in over 22,000 cosmetics as preservatives at concentrations up to 0.8% (mixtures of parabens) or up to 0.4% (single paraben). The group includes Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben. Industry estimates of the daily use of cosmetic products that may contain parabens were 17.76 g for adults and 378 mg for infants. Parabens in cosmetic formulations applied to skin penetrate the stratum corneum in inverse relation to the ester chain length. Carboxylesterases hydrolyze parabens in the skin. 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 not significantly toxic by various routes of administration. Subchronic and chronic oral studies indicate that parabens are practically nontoxic. Numerous genotoxicity studies, including Ames testing, dominant lethal assay, host-mediated assay, and cytogenic assays, indicate that the Parabens are generally nonmutagenic, although Ethylparaben and Methylparaben did increase chromosomal aberrations in a Chinese Hamster ovary cell assay. Ethylparaben, Propylparaben, and Butylparaben in the diet produced cell proliferation in the forestomach of rats, with the activity directly related to chain length of the alkyl chain, but Isobutylparaben and Butylparaben were noncarcinogenic in a mouse chronic feeding study. Methylparaben was noncarcinogenic when injected subcutaneously in mice or rats, or when administered intravaginally in rats, and was not cocarcinogenic when injected subcutaneously in mice. Propylparaben was noncarcinogenic in a study of transplacental carcinogenesis. Methylparaben was nonteratogenic in rabbits, rats, mice, and hamsters, and Ethylparaben was nonteratogenic in rats. Parabens, even at levels that produce maternal toxicity, do not produce fetal anomalies in animal studies. Parabens have been extensively studied to evaluate male reproductive toxicity. In one in vitro study, sperm were not viabile at concentrations as low as 6 mg/ml Methylparaben, 8 mg/ml Ethylparaben, 3 mg/ml Propylparaben, or 1 mg/ml Butylparaben, but an in vivo study of 0.1% or 1.0% Methylparaben or Ethylparaben in the diet of mice reported no spermatotoxic effects. Propylparaben did affect sperm counts at all levels from 0.01% to 1.0%. Epididymis and seminal vesicle weight decreases were reported in rats given a 1% oral Butylparaben dose; and decreased sperm number and motile activity in F1 offspring of rats maternally exposed to 100 mg/kg day- 1 were reported. Decreased sperm numbers and activity were reported in F1 offspring of female rats given Butylparaben (in DMSO) by subcutaneous injection at 100 or 200 mg/kg day- 1, but there were no abnormalities in the reproductive organs. Methylparaben was studied using rats at levels in the diet up to an estimated mean dose of 1141.1 mg/kg day- 1 with no adverse testicular effects. Butylparaben was studied using rats at levels in the diet up to an estimated mean dose of 1087.6 mg/kg day- 1 in a repeat of the study noted above, but using a larger number of animals and a staging analysis of testicular effects - no adverse reproductive effects were found. Butylparaben does bind to estrogen receptors in isolated rat uteri, but with an affinity orders of magnitude less than natural estradiol. Relative binding (diethylstilbesterol binding affinity set at 100) to the human estrogen receptors α and β increases as a function of chain length from not detectable for Methylparaben to 0.267 ± 0.027 for human estrogen receptor α and 0.340 ± 0.031 for human estrogen receptor β for Isobutylparaben. In a study of androgen receptor binding, Propylparaben exhibited weak competitive binding, but Methylparaben had no binding effect at all. PHBA at 5 mg/kg day-1 subcutaneously (s.c.) was reported to produce an estrogenic response in one uterotrophic assay using mice, but there was no response in another study using rats (s.c. up to 5 mg/kg day- 1) and mice (s.c. up to 100 mg/kg day- 1) and in a study using rats (s.c. up to 100 mg/kg day- 1). Methylparaben failed to produce any effect in uterotrophic assays in two laboratories, but did produce an effect in other studies from another laboratory. The potency of Methylparaben was at least 1000× less when compared to natural estradiol. The same pattern was reported for Ethylparaben, Propylparaben, and Butylparaben when potency was compared to natural estradiol. In two studies, Isobutylparaben did produce an estrogenic response in the uterotrophic assay, but the potency was at least 240,000× less than estradiol. In one study, Benzylparaben produced an estrogenic response in the uterotrophic assay, but the potency was at least 330,000× less than estradiol. Estrogenic activity of parabens and PHBA was increased in human breast cancer cells in vitro, but the increases were around 4 orders of magnitude less than that produced by estradiol. Parabens are practically nonirritating and nonsensitizing in the population with normal skin. Paraben sensitization has occurred and continues to be reported in the case literature, but principally when exposure involves damaged or broken skin. Even when patients with chronic dermatitis are patch-tested to a parabens mix, parabens generally induce sensitization in less than 4% of such individuals. Many patients sensitized to paraben-containing medications can wear cosmetics containing these ingredients with no adverse effects. Clinical patch testing data available over the past 20 years demonstrate no significant change in the overall portion of dermatitis patients that test positive for parabens. As reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel, the available acute, subchronic, and chronic toxicity tests, using a range of exposure routes, demonstrate a low order of parabens' toxicity at concentrations that would be used in cosmetics. Parabens are rarely irritating or sensitizing to normal human skin at concentrations used in cosmetics. Although parabens do penetrate the stratum corneum, metabolism of parabens takes place within viable skin, which is likely to result in only 1% unmetabolized parabens available for absorption into the body. The Expert Panel did consider data in the category of endocrine disruption, including male reproductive toxicity and various estrogenic activity studies. The CIR Expert Panel compared exposures to parabens resulting from use of cosmetic products to a no observed adverse effect level (NOAEL) of 1000 mg/kg day- 1 based on the most statistically powerful and well-conducted study of the effects of Butylparabens on the male reproductive system. The CIR Expert Panel considered exposures to cosmetic products containing a single parabens preservative (use level of 0.4%) separately from products containing multiple parabens (use level of 0.8%) and infant exposures separately from adult exposures in determining margins of safety (MOS). The MOS for infants ranged from ∼6000 for single paraben products to ∼3000 for multiple paraben products. The MOS for adults ranged from 1690 for single paraben products to 840 for multiple paraben products. The Expert Panel considers that these MOS determinations are conservative and likely represent an overestimate of the possibility of an adverse effect (e.g., use concentrations may be lower, penetration may be less) and support the safety of cosmetic products in which parabens preservatives are used.
Article
Parabens are used extensively in personal care products; however, their estrogenic properties have raised concern over risks to human health. High levels of total parabens, mainly as conjugates, have been reported in human plasma/serum, with limited data on native parabens. Our objective was to assess and link plasma concentrations of native common parabens to self-reported use of personal care products in women from the general population. The information was obtained from an extensive questionnaire on diet and lifestyle previously answered by the women in the NOWAC study. Plasma samples from 332 individuals were extracted and cleaned up by automated solid phase extraction and analyzed by ultra high performance liquid chromatography time-of-flight mass spectrometry. Native methyl paraben dominated and was detected in 63% of the samples, with a median level of 9.4 ng/ml. Ethyl paraben (median <3 ng/ml) and propyl paraben (median <2 ng/ml) were detected in 22 and 29%, respectively. Butyl and benzyl parabens were not detected. For the first time, elevated levels of native parabens are reported in women from the general population. The concentrations were significantly associated with the use of skin lotions, indicating that frequent (daily or more) use maintain elevated concentrations despite the parabens short half-lives. These findings clearly emphasize the need to study potential health effects in the general population.
Article
Clinical studies dating back decades report a disproportionately high number of female breast cancers originating in the upper outer quadrant of the breast [1], and although this is attributed to a greater amount of epithelial tissue in that region, it is also the area to which underarm cosmetic products are applied [2,3]. Early studies reported 31% of cancers in the upper outer quadrant [1], but later studies in the 1990s report up to 61% [2,3]. The annually recorded quadrant incidence of breast cancer in Britain documents a rise in England and Wales from 47.9% in the upper outer quadrant in 1979 to 53.3% in 2000, and in Scotland a rise from 38.3% in the upper outer quadrant in 1980 to 54.7% in 2001 [4]. Any increase in the disproportionality of breast cancer in the upper outer quadrant would be inconsistent with an explanation relating to the greater amount of target epithelial tissue in that region but does parallel the increasing use of cosmetics in the underarm area [2-5].
Article
Phthalate and phenol exposure is prevalent among the general population and of potential concern for pregnant women and children because of their suspected susceptibility to endocrine effects. To evaluate the extent of exposure to several phthalates and phenols in a sample of Spanish pregnant women - according to their individual characteristics (age, social class, education, and body mass index) - and children who participated in the INMA - Infancia y Medio Ambiente (Environment and Childhood) project. One spot urine sample was taken during the third trimester of pregnancy from 120 pregnant women and from 30 4-year old children belonging to 5 Spanish birth cohorts, and analyzed for 11 phthalate metabolites and 9 phenols. Three metabolites of di(2-ethylhexyl) phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-2-ethyl-5-hydroxyhexyl phthalate, and mono-2-ethyl-5-oxohexyl phthalate; two metabolites of dibutyl phthalates, mono-isobutyl phthalate and mono-n-butyl phthalate; monoethyl phthalate (MEP), the main metabolite of diethyl phthalate; and two phenols, methyl paraben (M-PB) and 2,5-dichlorophenol were detected in the urine samples of all women. The highest urinary concentrations were for MEP and M-PB. Urinary concentrations of all phthalate metabolites and of 2,4-dichlorophenol, 2,5-dichlorophenol, and bisphenol A were lower in the pregnant women than in the children. Among women, a positive relationship with social class and education was shown for most of the phthalate metabolites and phenols. Almost all phthalate metabolites varied by region even after adjusting for social class and education. Phthalate and phenol exposures are prevalent in a group of pregnant women and young children, two susceptible populations, and these exposures might be positively related to social class.
Article
Preservatives and fragrances are important and frequent skin sensitizers, found in a wide range of products intended for personal and occupational use. To examine the use of preservatives and fragrances in certain cosmetics and detergents on the market. The product types studied were shampoos, hair conditioners, liquid soaps, wet tissues, washing-up liquids, and multi-purpose cleaners. Ingredient labels of 204 cosmetic products and ingredient data sheets of 97 detergents, available on company websites, were examined. The preservatives most frequently identified were phenoxyethanol, methylparaben, sodium benzoate, propylparaben, and methylchloroisothiazolinone/methylisothiazolinone. Parabens were found in 44% of cosmetics and 9% of detergents; formaldehyde-releasers in 25% of cosmetics and 8% of detergents; and isothiazolinones in 23% of cosmetics and 28% of detergents. The fragrances most frequently identified were linalool, limonene, hexyl cinnamal, butylphenyl methylpropional, and citronellol. Eighty-eight per cent of the products contained fragrances, and any of the 26 fragrances requiring labelling were found in half of the cosmetics and one-third of the detergents. Several preservatives and fragrances with well-known skin-sensitizing potential were common in the examined product types. Such products may be used several times a day by consumers and workers.
Article
In order to assess potential risks of exposure to environmental chemicals, more information on concomitant exposure to different chemicals is needed. We present data on chemicals in human milk of a cohort study (2004, 2005, 2006) of 54 mother/child pairs, where for the first time, cosmetic UV filters, synthetic musks, parabens and phthalate metabolites were analyzed in the same sample along with persistent organochlor pollutants (POPs), i.e., organochlor pesticides and metabolites, polybrominated diphenylethers and polychlorinated biphenyls (PCBs). The two groups of chemicals exhibited different exposure patterns. Six out of seven PCB congeners and a majority of pesticides were present in all milk samples, with significant correlations between certain PCB congener and pesticide levels, whereas the cosmetic-derived compounds, UV filters, parabens and synthetic musks, exhibited a more variable exposure pattern with inter-individual differences. UV filters were present in 85.2% of milk samples, in the range of PCB levels. Comparison with a questionnaire revealed a significant correlation between use of products containing UV filters and their presence in milk for two frequently used and detected UV filters, 4-methylbenzylidene camphor and octocrylene, and for the whole group of UV filters. Concentrations of PCBs and organochlor pesticides were within ranges seen in Western and Southern European countries. For several POPs, mean and/or maximum daily intake calculated from individual concentrations was above recent US EPA reference dose values. Our data emphasize the need for analyses of complex mixtures to obtain more information on inter-individual and temporal variability of human exposure to different types of chemicals.
Article
Unlabelled: Many environmental compounds with oestrogenic activity are measurable in the human breast and oestrogen is a known factor in breast cancer development. Exposure to environmental oestrogens occurs through diet, household products and cosmetics, but concentrations of single compounds in breast tissue are generally lower than needed for assayable oestrogenic responses. Results presented here and elsewhere demonstrate that in combination, chemicals can give oestrogenic responses at lower concentrations, which suggests that in the breast, low doses of many compounds could sum to give a significant oestrogenic stimulus. Updated incidence figures show a continued disproportionate incidence of breast cancer in Britain in the upper outer quadrant of the breast which is also the region to which multiple cosmetic chemicals are applied. Conclusion: If exposure to complex mixtures of oestrogenic chemicals in consumer products is a factor in breast cancer development, then a strategy for breast cancer prevention could become possible.
Article
Parabens are used as anti-microbial preservatives in a range of consumer products, especially in cosmetics. In vitro and animal studies have shown weak estrogenic and other endocrine disrupting effects of parabens, including reduced testosterone levels in exposed male rats. The knowledge of paraben exposure, distribution and excretion in humans is limited. In this study we determined the concentration of five parabens; methyl-, ethyl-, n-propyl-, n-butyl- and benzylparaben in urine, serum and seminal plasma samples from 60 healthy Danish men. To conduct the study a sensitive and specific method using LC-MS/MS for simultaneous determination of the five parabens was developed for all three different matrices. Highest concentrations of the parabens were found in urine, wherein methyl-, ethyl-, n-propyl- and n-butyl parabens were measurable in 98%, 80%, 98% and 83% of the men, respectively. Benzyl paraben was only measurable in urine from 7% of the men. Methyl- and n-propyl parabens were also measurable in the majority of serum and seminal plasma samples, whereas the other parabens could only be detected in some of the samples. In all the three matrices significant correlations between the parabens were seen. Furthermore, urinary paraben concentrations correlate to the paraben concentrations in both serum and seminal plasma.
Article
The diagnostic distribution and the relation between diagnosis and symptoms, symptom duration, tumour site, tumour size and breast size were studied in 1 244 women with breast symptoms examined at a special breast tumour clinic. 9% of the women had cancer, 62% fibroadenosis and 6% fibroadenoma. In 18% no breast disease was found. A painful tumour was experienced by 19% of all women with breast cancer, but by 54% of breast cancer patients below 50 years of age. 50% of the patients with fibroadenosis had a painful tumour. This symptom was thus not a discriminating feature between cancer and fibroadenosis in younger women. The reason that most breast tumours, both benign and malignant, are located in the upper outer quadrant is not known. It has been proposed that this might be due to the larger volume of this quadrant as compared with the others. The present results contradict this view.
Article
A reliable method for the extraction of steroid hormones from human uterine tissue and the subsequent measurement of these hormones in the subcellular compartments by radioimmunoassay is described. Extraction of radioactive steroid hormones from in vivo labelled human uterine tissue by different methods reveals that an almost quantitative extraction of steroid hormones from the nuclear fraction is obtained by sonication in ethanol-acetone. Extraction of steroid hormones with diethylether from a high speed cytosol is incomplete. Using a more potent denaturating agent prior to extraction with diethyl ether leads to complete extraction of unconjugated steroids.
Article
The inadvertent estrogenicity of certain synthetic chemicals, and their subsequent effects on the endocrine system of humans and wildlife, is of concern. In this paper we report findings from in vitro and in vivo (uterotrophic) studies which confirm that a range of alkyl hydroxy benzoate preservatives (parabens) are weakly estrogenic. In a receptor-binding assay, butylparaben was able to compete with 3H-estradiol for binding to the rat estrogen receptor with an affinity approximately 5 orders of magnitude lower than that of diethylstilboestrol, and between 1 and 2 orders of magnitude less than nonylphenol. In an in vitro yeast-based estrogen assay, the four most widely used parabens (namely methyl-, ethyl-, propyl-, and butylparaben) were all found to be weakly estrogenic with the most potent (butylparaben) being 10,000-fold less potent than 17 beta-estradiol. The estrogenic activity of parabens was inhibited by 4-hydroxy tamoxifen in vitro, illustrating the requirement of these chemicals to interact with the estrogen receptor in order to activate the yeast. When administered orally to immature rats, the parabens were inactive. However, subcutaneous administration of butylparaben produced a positive uterotrophic response in vivo, although it was approximately 100,000 times less potent than 17 beta-estradiol. Given their use in a wide range of commercially available topical preparations, it is suggested that the safety in use of these chemicals should be reassessed, with particular attention being paid to estimation of the actual levels of systemic exposure of humans exposed to these chemicals. The acquisition of such data is a prerequisite to the derivation of reliable estimates of the possible human risk of exposure to parabens.
Article
Breast cancer is the commonest cause of cancer death in women worldwide. Rates vary about five-fold around the world, but they are increasing in regions that until recently had low rates of the disease. Many of the established risk factors are linked to oestrogens. Risk is increased by early menarche, late menopause, and obesity in postmenopausal women, and prospective studies have shown that high concentrations of endogenous oestradiol are associated with an increase in risk. Childbearing reduces risk, with greater protection for early first birth and a larger number of births; breastfeeding probably has a protective effect. Both oral contraceptives and hormonal therapy for menopause cause a small increase in breast-cancer risk, which appears to diminish once use stops. Alcohol increases risk, whereas physical activity is probably protective. Mutations in certain genes greatly increase breast-cancer risk, but these account for a minority of cases.
Article
Parabens are a group of compounds widely used as preservatives in foodstuffs, cosmetics, toiletries and pharmaceuticals. These compounds are known to exert a weak estrogenic activity, with butylparaben showing the most potent activity among methyl-, ethyl- and propyl esters in in vitro recombinant yeast assay and in in vivo uterotrophic assay. To account for potential reproductive effects in male animals, butylparaben was administered to 3-week-old Wistar rats divided in groups of eight subjects, at doses of 0.00%, 0.01%, 0.10% and 1.00% with the animal's diet. After 8 weeks, the rats were killed by decapitation and the weights of the testes, epididymides, prostates, seminal vesicles and preputial glands were recorded. The absolute and relative weights of epididymides were decreased in a dose-dependent manner and the decrease was statistically significant at 0.10% and above. The cauda epididymal sperm reserve of all treated groups was significantly decreased. The sperm count of the group receiving the highest dose was 58.2% of control values. The daily sperm production (DSP) in the testis was also significantly lower in all treated groups when compared to controls. Serum testosterone concentration was lowered dose-dependently and was significant at 0.1% or more. The daily intake of butylparaben that caused these disruptions is similar to the lower level of acceptable daily intake (ADI) for parabens in the European Community (EC) and in Japan. The results of the present experiments show for the first time that exposure of a postweaning mammal to butylparaben had an adverse effect on the secretion of testosterone and in the functions of the male reproductive system.
Article
Parabens are alkyl ester compounds of p-hydroxybenzoic acid widely used as preservatives in foodstuffs, cosmetics, toiletries and pharmaceuticals. These compounds are known to exert a weak estrogenic activity in estrogen receptor assays in vitro and in uterotrophic assays in vivo. In this paper, we have shown that butyl paraben had an adverse effect on the male mouse reproductive system and that it damaged the late steps of spermatogenesis in the testis. Butyl paraben was administered to 4-week-old Crj:CD-1 mice assigned to groups of eight animals, at doses of 0.01%, 0.10%, and 1.00% in the diet for 10 weeks. The average butyl paraben intake from the calculated food consumption was 14.4+/-3.60, 146+/-35.9, and 1504+/-357 mg/kg per day for the 0.01%, 0.10%, and 1.00% dietary butyl paraben groups, respectively. There were no treatment-related effects of butyl paraben on the liver, ventral prostates, seminal vesicles, and preputial glands (both in terms of absolute weight and relative to body weight) in any of the study groups. Both the absolute and relative weights of the epididymides were significantly higher in 1.00% group when compared with controls. A dose-dependent decrease of both round and elongated spermatid counts in stages VII-VIII seminiferous tubules was observed, and the elongated spermatid counts were significantly lower in all of the treated groups. The numbers of spermatogonia and spermatocytes did not differ from control values. The serum testosterone concentration decreased in a dose-dependent fashion and was significant at 1.00%. These data demonstrated that butyl paraben can exert an adverse effect on the male reproductive system at doses that are well below those of the accepted daily intake (ADI) in Japan.
Article
Parabens are p-hydroxybenzoic acid ester compounds widely used as preservatives in foods, cosmetics, toiletries and pharmaceuticals. These compounds exert a weak estrogenic activity as determined by in vitro estrogen receptor assay and in vivo uterotrophic assay. In a previous study, it was demonstrated by the present author that exposure of post-weaning mammals to butyl paraben adversely affects the secretion of testosterone and the function of the male reproductive system. In the present study, it is shown that propyl paraben also adversely affects the hormonal secretion and the male reproductive functions. Propyl paraben was administered to 3-week-old rats which were divided into four groups of eight animals each, at doses of 0.00, 0.01, 0.10 and 1.00% with the AIN93G modified diet. At the end of 4 weeks, the rats were sacrificed by decapitation and the weights of testes, epididymides, prostates, seminal vesicles and preputial glands were determined. There were no treatment-related effects of propyl paraben on the organ weights in any of the study groups. The cauda epididymal sperm reserves and concentrations decreased in a dose-dependent manner and the difference was significant at dose of 0.10% and above. Daily sperm production and its efficiency in the testis of all groups receiving propyl paraben significantly decreased. The serum testosterone concentration decreased in a dose-dependent manner and the decrease was significant in the group that received the highest dose. The exposure level at which this effect was observed is the same as the upper-limit acceptable daily intake (10 mg/kg body weight/day) of parabens in the European Community and Japan.
Article
Oestrogens are heavily implicated in the risk to, and progression of, breast cancer. Therapeutic strategies targeted at the oestrogenic stimulus to the breast and hormone-sensitive breast cancers are extremely attractive measures both to prevent the disease and to treat established tumours. The present review outlines the biological rationale for such endocrine therapy and traces the evolution whereby irreversible surgical procedures have been replaced by potent and specific drugs. In particular, the development of the latest generation of agents which inhibit oestrogen biosynthesis (aromatase inhibitors) is considered by defining the central role of the aromatase enzyme, its regulation and contribution to circulating and tumour endogenous oestrogens. The nature of response and resistance which may be elicited following the use of endocrine therapy is also described as this may determine the optimal use of aromatase inhibitors and, more generally, anti-hormone therapy in the management of women at high risk to, or with, breast cancer.
Article
Although risk factors are known to include the loss of function of the susceptibility genes BRCA1/BRCA2 and lifetime exposure to oestrogen, the main causative agents in breast cancer remain unaccounted for. It has been suggested recently that underarm cosmetics might be a cause of breast cancer, because these cosmetics contain a variety of chemicals that are applied frequently to an area directly adjacent to the breast. The strongest supporting evidence comes from unexplained clinical observations showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast, just the local area to which these cosmetics are applied. A biological basis for breast carcinogenesis could result from the ability of the various constituent chemicals to bind to DNA and to promote growth of the damaged cells. Multidisciplinary research is now needed to study the effect of long-term use of the constituent chemicals of underarm cosmetics, because if there proves to be any link between these cosmetics and breast cancer then there might be options for the prevention of breast cancer.
Article
In the decade that has elapsed since the suggestion that exposure of the foetal/developing male to environmental oestrogens could be the cause of subsequent reproductive and developmental effects in men, there has been little definitive research to provide conclusions to the hypothesis. Issues of exposure and low potency of environmental oestrogens may have reduced concerns. However, the hypothesis that chemicals applied in body care cosmetics (including moisturizers, creams, sprays or lotions applied to axilla or chest or breast areas) may be affecting breast cancer incidence in women presents a different case scenario, not least in the consideration of the exposure issues. The specific cosmetic type is not relevant but the chemical ingredients in the formulations and the application to the skin is important. The most common group of body care cosmetic formulation excipients, namely p-hydroxybenzoic acid esters or parabens, have been shown recently to be oestrogenic in vitro and in vivo and now have been detected in human breast tumour tissue, indicating absorption (route and causal associations have yet to be confirmed). The hypothesis for a link between oestrogenic ingredients in underarm and body care cosmetics and breast cancer is forwarded and reviewed here in terms of: data on exposure to body care cosmetics and parabens, including dermal absorption; paraben oestrogenicity; the role of oestrogen in breast cancer; detection of parabens in breast tumours; recent epidemiology studies of underarm cosmetics use and breast cancer; the toxicology database; the current regulatory status of parabens and regulatory toxicology data uncertainties. Notwithstanding the major public health issue of the causes of the rising incidence of breast cancer in women, this call for further research may provide the first evidence that environmental factors may be adversely affecting human health by endocrine disruption, because exposure to oestrogenic chemicals through application of body care products (unlike diffuse environmental chemical exposures) should be amenable to evaluation, quantification and control. The exposure issues are clear and the exposed population is large, and these factors should provide the necessary impetus to investigate this potential issue of public health.