Parabens is a preservative class widely used in cosmetic and pharmaceutical products. Chemically, they are a series of parahidroksibenzoat or a parahidroksibenzoat acid ester (also known as 4-hydroxybenzoic acid). Parabens are effective preservatives in many types of formulas. These compounds, and their salts, are used primarily for their bactericidal and fungicidal properties. They are found in shampoos, commercial moisturizers, shaving gel, personal lubricants, topical/parenteral medicines, spray solution, makeup, and toothpaste. They are also used as food additives.
Their success as preservatives, in combination with low cost, long history of use, and the ineffectiveness of some natural alternatives such as grape seed extract (GSE), may explain why parabens are very common. There is no effective direct relationship between paraben and cancer that has been established.
Video Paraben
Mode aksi
Parabens are active against a wide spectrum of microorganisms. However, their antibacterial way of working is not well understood. They are considered to act by disrupting the membrane transport process or by inhibiting the synthesis of DNA and RNA or some of the key enzymes, such as ATPase and phosphotransferase, in some bacterial species. Propylparaben is thought to be more active against most bacteria than methylparaben. Stronger antibacterial action of propylparaben may be due to greater solubility in the bacterial membrane, allowing it to reach the cytoplasmic target in larger concentrations. However, since most studies on parabens work mechanisms show that their antibacterial action is linked to the membrane, it is possible that greater lipid solubility disrupts the lipid bilayer, thus disrupting the transport process of bacterial membranes and possibly causing leakage of intracellular constituents.
Maps Paraben
Chemistry
Parabens is the ester of the the -hydroxy ben zoic acid, from which the name is derived. Common parabens include methylparaben (E number E218), ethylparaben (E214), propylparaben (E216), butylparaben and heptylparaben (E209). Less common parabens include isobutylparaben, isopropylparaben, benzylparaben and their sodium salts. The general chemical structure of the parabens is shown on the top right of this page, where R represents alkyl groups such as methyl, ethyl, propyl or butyl.
Synthesis
All parabens used commercially are synthetically manufactured, although some are identical to those found in nature. They are produced by esterifying the -hydroxybenzoic acid with an appropriate alcohol, such as methanol, ethanol, or n-propanol. -Hydroxybenzoic acid is in turn produced industrially from Kolbe-Schmitt reaction modification, using potassium phenoxide and carbon dioxide.
Health considerations
Most of the available paraben toxicity data comes from a single exposure study, which means one type of paraben in one type of product. According to the paraben study, this is relatively safe, posing only an insignificant risk to the endocrine system. However, since many types of parabens in many types of products are used generally, further assessment of the additives and cumulative risks of dual paraben exposure from daily use of various cosmetic and/or personal care products is required.
Allergic reactions
In individuals with normal skin, parabens, for the most part, do not cause irritation and do not cause sensitization. Parabens can, however, cause skin irritation and contact dermatitis and rosacea in individuals with paraben allergies, a small percentage of the general population.
Breast cancer
There is no evidence to suggest that consumer product applications containing parabens cause cancer. Investigations by the American Cancer Society and FDA found that the current paraben rate in consumer products is not harmful. A 2005 review concluded "it is biologically unreasonable that parabens can increase the risk of estrogen-mediated endpoints, including effects on the male reproductive tract or breast cancer" and that "the worst daily exposure to parabens would pose much less risk than the exposure to naturally occurring endocrine chemicals in diets such as daidzein phytoestrogens. "
Estrogenic activity
Animal experiments show that parabens have weak estrogen activity, acting as xenoestrogens. In an in vivo study, the effect of butylparaben was determined to be about 1/100,000th of estradiol, and was only observed at dose levels about 25,000 times higher than the level normally used to maintain the product.. The study also found that the in vivo activity of parabens estrogenic was reduced by about threefold compared with in vitro activity .
The estrogenic activity of parabens increases with the length of the alkyl group. It is believed that propylparaben is estrogenic to some extent, although it is expected to be less than butylparaben based on its less lipophilic nature. Since it can be concluded that the butylparaben estrogenic activity is negligible in normal use, the same must be inferred for a shorter analogue because the estrogenic activity of the parabens increases with the length of the alkyl group.
Sun exposure
Studies show that methylparaben applied to the skin can react with UVB leading to increased skin aging and DNA damage.
Rule
The European Scientific Committee on Consumer Safety (SCCS) reaffirms in 2013 that methylparaben and ethylparaben are safe at maximum permissible concentrations (up to 0.4% for one ester or 0.8% when used in combination). SCCS concludes that the use of butylparaben and propylparaben as preservatives in cosmetic products is thus safe for consumers, as long as the amount of concentration each does not exceed 0.19%. Isopropylparaben, isobutylparaben, phenylparaben, benzylparaben and pentylparaben are prohibited by Commission Regulation (EU) No 358/2014.
Controversy
A paper in 2004 led to a discussion of the possible carcinogenicity and estrogenic effects expressed on the continuous use of parabens as a preservative.
The mainstream cosmetics industry believes that parabens, like most cosmetic ingredients, are safe based on long-term use and safety records and the latest scientific studies. Public interest organizations that raise awareness about cosmetic ingredients believe that more research is needed to determine the safety of parabens, under the precautionary principle. Concerns about endocrine disruptors have led consumers and companies to seek paraben free alternatives. Grapefruit seed extract was promoted as a natural preservative, but in one study, five of the six commercial products tested were found to contain preservatives such as methylparaben and benzethonium chloride. A common alternative is phenoxyethanol, but this has its own risks and has led to FDA warnings on inclusions in nipple creams.
Environmental considerations
Releasing to the environment
The discharge of parabens into the environment is common because of their common use everywhere in cosmetic products. A 2010 study on personal care products available by consumers revealed that 44% of the products tested contained parabens. When washing these products from the human body, they flow into the sewer and into the community's waste water. Once this happens, the potential of parabens accumulates in aqueous and solid medium to materialize. Some of the most common paraben derivatives found in the environment include methylparaben, ethylparaben, propylparaben, and butylparaben. Parabens flow from waste water to wastewater treatment plants (IPAL) as influent where they are disposed, chemically altered, or released into the environment through mud or tertiary waste.
In one New York WWTP, the mass load of all paraben paraben derivatives (methylparaben, ethylparaben, propylparaben, butylparaben, etc.) of the influent wastewater was found to be 176 mg, mg/day/1000 persons. When this value is used to estimate the number of parabens entering WWTP of the 8.5 million people who currently live in New York City for a full year, a value of about 546 kg of parabens is calculated. Therefore, the level of paraben accumulation has been shown to be significant in long-term adherence. WWTP removes about 92% -98% of paraben derivatives; However, many of these removals are caused by the formation of degradation products. Despite the well-known high elimination through WWTP, various studies have measured the high levels of paraben derivatives and environmental degradation products.
Formation of degradation products
Chlorinated Products
In addition to the parent parabens, paraben degradation products formed throughout the WWTP stage cause environmental concerns, including mono and chlorinated parabens. When a paraben-containing product is washed in vain, the paraben has the potential to experience a chlorination reaction. This reaction can occur with the presence of free chlorine in tap water or with sodium hypochlorite, which is often used in WWTP as a final disinfectant step. In neutral water, Raman spectroscopy has confirmed that dominant chlorine is present as hypochlorite acid (HClO). Parabens can react with HClO to form mono and chlorinated products via electrophilic aromatic substitution. Electrophilic attacks of chlorine form a carbocation stabilized by the density of electrons donated from the paraben hydroxyl group. This step is endergonic because of the loss of aromaticity, although the hydroxyl group acts as an activating group that increases the rate. The base can then abstract protons from the chlorine-containing carbon, followed by subsequent aromatic restorations by the pi electrons involved. Because the hydroxyl group is more active than the ester group of the parabens, the reaction will be directly on both ortho positions, since the positions are already blocked.
The Arrhenius equation was used in the study to calculate the activation energy for chlorination of four parabens (methyl-, ethyl-, propyl-, and butylparaben) and was found to be in the range of 36 kJ/mol - 47 kJ/mol. In another study, tap water at 20 Â ° C (68 Â ° F) containing 50-200 chlorine chloride was spiked with 0.5 Ã,ÂμM propylparaben and mixed compositions monitored for 40 min to determine whether chlorination occurred under conditions found in tap water. Results of the study confirmed the loss of propylparaben after 5 min, the appearance of 3-chloro-propylparaben and 3,5-dichloro-propylparaben paraben by 5 min, and persistence of 3,5-dichloro-propylparaben as the main species left in the reaction. A similar trend, although faster, was found in studies where the reaction temperature increased to 35 ° Celsius. <4> 4-hydroxybenzoic acid (PHBA) <4>
Other significant paraben degradation products include 4-Hydroxybenzoic acid (PHBA). There are two mechanisms in which the paraben can lower to the PHBA. The first degradation route occurs chemically. Parab parabens is ready to undergo the hydrolysis of catalyzed ester bonds, forming a PHBA. The reaction occurs under moderate bases, especially when pH >> 8. This reaction is quite common in household environments because the pH range of household wastewater is 6-9 and the presence of parabens in cosmetic products. When cosmetic products containing parabens are thrown into the wastewater effect of the community, they become exposed to an environment where pH> = 8, and the catalyst-base hydrolysis of the paraben parent occurs, forming a PHBA.
In the electron transfer mechanism, pi electrons in a double bond between oxygen and carbonyl carbon resonate with oxygen, leaving a negative charge on oxygen and a positive charge on carbonyl carbon. Hydroxide ions, acting as nucleophiles, invade carbonyl carbonyl now electrophilic, resulting in hybridization of sp 3 on carbonyl carbon. The electrons resonate again to form a double bond between oxygen and carbonyl carbon. To maintain hybridization sp 2 , the -OR group will exit. The -OR group acts as a better leaving group than the -OH group because of its ability to maintain negative charges with greater stability. Finally, -OR-, acting as a base, will deprotonize carboxylic acids to form carboxylic anions.
The second way in which the paraben can decrease to PHBA occurs biologically in WWTP. During the secondary clarifier phase of Wastewater treatment, sludge accumulates at the bottom of the secondary clarifier. After the separation of the liquid and solid phases of the influent entering, parabens have a greater tendency to accumulate in the sludge. This is due to its moderate hydrophobicity, as measured by the log value of K ow about 1.58. This mud is concentrated in organic nutrients; consequently, the proliferation of microorganisms becomes common in the mud. One organism is Enterobacter cloacae , which biologically metabolizes slabge parabens to the PHBA.
Accumulated degradation products in an environment
Through various analytical techniques such as Gas chromatography and high performance liquid chromatography, the exact rate of accumulation of paraben derivatives and degradation products in the environment has been quantified. This level has been accurately measured in tertiary waste and sewage sludge, as this is the main road through which their parabens and degradation products reach the environment after being removed from WWTP.
The stability of parabens in waste sludge is relatively high because of their ability to bind organic materials. The value of the soil adsorption coefficient was calculated by the US Environmental Protection Agency of 1.94 (methylparaben), 2.20 (ethylparaben), 2.46 (propylparaben), and 2.72 (butylparaben), all of which show that the parabens have the ability to adhere to organic from sediment and sludge, and thus, survive in the environment.
The chlorinated paraben is removed from the WWTP with an efficiency of only 40% compared to 92-98% paraben parent efficiency. The decrease in removal efficiency can be attributed to the decreased biodegradability of chlorinated parabens, increased overall stability across the IPAL, and relatively low absorption to the mud phase due to low log K ow values.
Higher PHBA rates are found in tertiary waste compared with paraben derivatives, and PHBA exists in the highest concentration in sewage sludge. There are two reasons for this level of accumulation. The first reason is the tendency of PHBA to absorb solid particles, which can be estimated by benzoic acid with a value of K d about 19. PKa PHBA is 2.7, but is in a pH environment. between 6-9. Since pKa is less than pH, carboxylic acids will be deprotonated. The carboxylate enables it to act as an absorber in a dense environmental matrix, thus encouraging its aggregation in tertiary waste, but especially sewage sludge, acting as the solid matrix itself. The second reason is due to the intermediate increase in the PHBA level during the secondary clarifier phase of the WWTP through biological processes.
Environmental issues with paraben degradation products
Several studies have linked chlorinated parabens to endocrine disrupting functions, particularly mimicking the effects of Estrogen, and chlorinated parabens are believed to be 3-4 times more toxic than their parent parabens. In Daphnia magna , the general toxicity given by chlorinated parabens occurs through impaired non-specific cell membrane function. The potential of chlorinated parabens correlates with the tendency of the compound to accumulate in the cell membrane. Thus, chlorinated parabens generally increase toxicity as their ester chains increase in length due to their hydrophobic increase.
The implications of PHBA environmental accumulation also ensure attention. If tertiary effluents are reused for community use as Greywater, it poses a danger to humans. These hazards include, but are not limited to, abnormal fetal development, endocrine disruptive activity, and the effects of promoting inappropriate estrogen. If tertiary effluents are released to the environment in rivers and streams or if mud is used as fertilizer, it poses a danger to environmental organisms. It is highly toxic to these organisms at lower trophic levels, especially algae species. In fact, it has been shown that LC 50 for certain algae species, Selenastrum capricornutum , is 0.032 microgram/L. This is less than the abundance of natural PHBA in tertiary waste at the 0.045 level? G/L, thus indicating that current PHBA levels in tertiary waste could potentially wipe out more than 50% of Selenastrum capricornutum associated with.
Parabens removal by ozonation
Ozonation is an advanced treatment technique that has been considered a possible method to limit the number of parabens, chlorinated parabens, and PHBAs that accumulate in the environment. Ozone is a very powerful oxidant that oxidizes parabens and makes it easier to remove after passing the filter. Due to the electrophilic ozone properties, it can easily react with aromatic paraben rings to form hydroxylated products. Ozonation is generally regarded as a less harmful disinfection method than chlorination, although ozonation requires more cost consideration. Ozonation has shown great efficacy in parabens removal (98.8-100%) and its efficacy is slightly lower than 92.4% for PHBA. A slightly lower rapture rate, however, was observed for chlorinated parabens (59.2% -82.8%). The proposed reaction mechanism for eliminating parabens by ozonization is mechanically detailed.
References
Source of the article : Wikipedia
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