Comprehensive Effects of Parabens in Human Physiology Seeham Ali Qasim Alkafajy1*, and Rawaa Abdul-Ameer Abdul-Jabbar1 1. Dept of Biology, College of Science, Mutansiriyah University, Iraq *Corresponding author: [email protected] Abstract:- Parabens are industrial chemicals that have been widely applied as preservatives for many products, such as cosmetics, medicines and foodstuffs, due to their ability to extend the life of products and prevent pathogenic bacteria and mold from developing them. Paraben compounds include methylparaben, ethylparaben, propylparaben, butylparaben, heptylparaben and benzyl-paraben.P-hydroxybenzoic acid is the main receptor of parabens in the human body, recently, it has been observed these compounds are present in blood serum and urine in different concentrations after multiple and long-term exposure to parabens as it is absorbed through the skin due to the ability of parabens to dissolve in water. Also, the increased ability of parabens to penetrate the skin depends on their structures, length of ester side chains, and the type of volatile solvents such as acetone and ethanol. Academic studies have also proven the presence of these chemical compounds in the breast tissue of breast cancer patients, as the estrogenic properties of parabens may play a role in the development of breast cancer that has raised public concern about their use. Other studies have confirmed that parabens are classified among substances that cause endocrine function disruption, such as the thyroid and adrenal glands. On the other hand, researches indicated that women who have a high concentration of polyethylene paraben suffer from short menstrual periods and poor fertility, and current studies conducted on male rats have found that parabens negatively affect the function of the male reproductive system by reducing the concentration of sperm, reducing the level of testosterone secretion in their serum and comprehensively affects the quality of semen in males. Keywords: Parabens, human physiology, industrial chemicals How to cite this article: Alkafajy SAQ, Abdul-Jabbar RAA (2020): Comprehensive effects of parabens inhuman physiology, Ann Trop Med & Public Health; 23(S20): SP232242. DOI: http://doi.org/10.36295/ASRO.2020.232242 Introduction Parabens are preservative compounds in processed foods, toothpaste, shampoos, topical/parenteral pharmaceuticals pharmaceutical products and cosmetics utilized to inhibit the growth of microorganisms, hence, extending the life of products having these chemicals. On the other hand, chemically are defined as a family of chemicals that are series of alkyl esters or salts of para-hydroxybenzoic acid (PHBA) that Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.232242 occurs naturally in many vegetables and fruits, like blueberries, cherries, onions and carrots, also naturally formed in the human body by the breakdown of some amino acids, etc (1,2) . As a result of high exposure to large amounts of Parabens, the human body quickly changes Parabens into natural PHBA and eliminates them, and this is confirmed by many studies that indicate that large percentage of it has been removed by urination within 24 hours(3, 4,5), Abbas and his colleagues in 2010 confirmed that in their study (6), it has no effect on the liver, but it could be detected in human plasma (4), milk (7) urine (3), and seminal (4), bio monitoring data could help scientists to determine who been exposed to higher levels of parabens depending on age, sex, and race (8,9). This substance has numerous beneficial characteristics such as resistance to hydrolysis, chemical stability within a wide range of pH and temperature, high water solubility, low frequency of sensitization or irritation, low production cost (10). Physico - Chemical characters of parabens :- Parabens are group of esters of para-hydroxybenzoic acid figure (1), the R symbol is represented an alkyl group such as ethyl, propyl, methyl, butyl, and heptyl which are known as ethylparaben (E214), propylparaben (E216), methylparaben (E218), heptylparaben (E209) and butylparaben respectively (11), the alkyl group ( alkyl chains) differ only in the length and branching, depending on these characteristics, however its solubility in water and log Kow (lipophilicity) will change between the types of paraben, is based on the length of the carbon chain of the alkyl group figure 1, researcher found increasing of the carbon chain cause decreasing water solubility, raising log Kow (lipophilicity), and boosting antimicrobial activity (12). Figure 1 General chemical structure of Parabens These substances differ in their Physicochemical characteristics such as molecular weight, melting point, boiling point, pKa, the ability to solube in water in different temperatures and the ability to solube in ethanol, are presented in Table 1 (10, 13, 14). Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.232242 Table 1 Physicochemical characteristic of the common paraben types. type ethylparaben propylparaben methylparaben heptylparaben butylparaben Particular weight 166.17g/mol 180.2 g/mol 152.15 g/mol 236.307g/mol 194.23g/mol melting point 116 °C 97.0 °C 131°C 49-51°C 68-69 °C boiling point 297-298 °C 294 - 295 °C 270-280°C 338.77°C - pKa 8.22 8.35 8.4 8.5 8.37 solubility in water 0.17 0.05 0.25 mg/L 0.02 mg/ml 0.02 at 25 °C, g/100 mL solubility in water 0.86 0.30 2.00 - 0.15 at 80 °C, g/100 mL solubility in ethanol 41 50 32 - 68 In general, Paraben types are hygroscopic crystals or powders have no taste, smell or colour and for these properties are used in the food and cosmetic industry because it does not change the nature of the product in terms of colour, taste, aroma and density (14, 10). Biosynthesis of parabens:- Parabens are an organic chemical which can be acquired naturally and synthetically, naturally produced by the esterification of para-hydroxybenzoic acid (15, 16) , that exists naturally in many plants (such as cherries, cucumbers, carrots, onions, Japanese honeysuckle, cocoa, vanilla, strawberries and blueberries), microorganisms (such as microbulbifer bacterium) and also formed in the human body by the breakdown of some amino acids (17), while industrially produced by the esterification of para-hydroxybenzoic acid with alcohols analogical (18) as in the chemical equation below C7H6O3 + ROH= C7H5O3R + H2O The symbol R represents CH3, C2H5, C3H7, C4H9, and this chemical formula C7H5O3R represent methylparaben, ethylparaben, propylparaben, butylparaben respectively (18), and know new manufacture technologies to save cost and energy during the manufacturing process of parabens by utilizing catalysts as microwave radiation and inorganic salts. Metabolism of parabens in human body Parabens as they’re widely used nowadays in food, cosmetics, and health products including drugs, there is an increased percentage of the potential side effects due to exposure of our bodies to large amount these substances. Its’ bioavailability is seen less in petrolatum preparation and much more in oil-in-water ones. The absorption is mainly percutaneous and it’s changeable according to the used surfactants. The parabens’ absorption is also affected by the oil/water phases of the formulation. Mostly all parabens consider are Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.232242 hydro- or lipophilicity, and have stability over a large pH range, (19) as many studies that confirmed that parabens compound are rapidly absorbed, metabolized and excreted from the body, 70% by urination, 4% by faeces, 2%were retained in the tissues and carcasses(20), but it cannot fully metabolize, and Aubert and his colleagues in 2012 added that all administration routes (oral, topical or subcutaneous administration) could enter the systemic circulation and give a single peak in the plasma and not accumulated in the tissues (20), but another study has proven that there is an accumulation of this substance in the different types of tissue such as brains, umbilical cords, and uteri (21), also study done by Xue and his colleagues in 2015 included marine creature include polar bears from the Chuckchi Sea and the Beaufort Sea found that trace concentrations of methylparaben in their livers (22,23), and Xue and Kannan in 2016 study also found trace concentrations of methylparaben in the tissues of albatrosses in Northwestern Pacific Ocean in Midway Atoll (24), parabens hydrolyzed into para-hydroxybenzoic acid (PHBA) and alcohol, in the liver, microsomes, small intestine, and in the skin of the mammals by esterases enzymes(21), and finally excreted as sulfate, glycine, and glucuronide conjugates by urination (23), and Kang and his colleagues in 2016 (5), explained that the concentration of parabens residues in urine differs between different populations and these differences due to the applicable laws of the countries regarding the maximal permissible concentration of parabens in the products. Health implications of parabens:- Parabens are found in a variety of products, have also been detected in urine and blood samples in the different populations, and concerns have been raised it can affect human health, over the last years, parabens have become huge buzzwords in the beauty, although individual products may contain limited amounts of parabens within safe limits set by the U.S. Food & Drug Administration (FDA), however, there’s a chance that parabens products harmful due to cumulative exposure of this substance, may cause