There is a need for the development of a safe and effective mouth sanitizer
Ideal oral personal care products (PCP) properties
Among the most important properties, the oral sanitizer should have cleansing, non-sensitizing, enhancing mucosa immune system, providing suitable hygiene with antiseptic actions and having acceptable safety profile properties.
The previous oral PCP
The present oral PCP are available mostly in the form of toothpastes and mouthwashes.
These products contain plenty of synthetic organic compounds, pharmaceutical ingredients, as well as some heavy metals and toxic minerals. These substances represent the majority of the unrecognized or emerging environment pollutants in everyday urban activities resulting in contaminated sediments and subsequently, far-reaching dispersal into aquatic environments (Edwards & Kjellerup, 2013).
Many PCP contain harmful substances including surface active agents (surfactants), antimicrobials, artificial colors, synthetic fragrance, and solvents, and preservatives (Pietrogrande & Basaglia, 2007).
Surfactants, also called detergents, are important ingredients in some toothpastes and mouthwashes and can be divided into amphoteric, cationic, anionic surfactants and non-ionic surfactants.
A study was conducted to evaluate the cytotoxic susceptibility using the MTT cytotoxicity assay using human keratinocyte for all surfactants. Cationic surfactant (benzalkonium chloride) showed the highest toxicity. Anionic (sodium lauryl sulfate) and amphoteric (cocamidopropyl betaine) surfactants showed similar moderate cytotoxicity. The non-ionic surfactant (polysorbate 20) showed the least toxic effect among all surfactants (Ward et al., 1998).
Cationic surfactants, such as benzalkonium chloride (BAC), are known as the highest dangerous compounds for the ecosystem. BAC is known to be toxic towards the Gram-negative bacteria Vibrio fischeri and Pseudomonas putida, and towards algae such as Chlorella vulgaris and Isochrysis galbana and Chaetoceros gracilis. BAC also showed genotoxic properties in mammalian and plant cells (Lavorgna, et al., 2016)
Anionic surfactant, such as sodium lauryl sulfate (SLS), sodium laureth sulfate (SLES), ammonium lauryl sulfate (ALS), and sodium pareth sulfate are very effective foaming agents. These surfactants are mostly used in many oral mouthwash and toothpaste products . In fact, SLS can act as a cleaning and emulsifying agent and is incorporated in the formulation of more than 90 percent of personal care and cleaning products mainly as foaming agents. These surfactants are used in high concentrations and may act as a potent local irritant. These surfactants are capable of damaging the mucosa and even the intact skin. They can penetrate deeply and are absorbed by the internal organs causing serious damages. The estimated blood parameters can potentially serve as biomarkers for assessing their toxicity (Wadaan & Mubarak, 2009; Fernandes et al., 2011). The penetration of SLS through mucosa and skin was found to increase with the increase in tap water temperature which increased the risk of developing irritant contact reactions (Emilson et al., 1993). Studies with human volunteers showed that several adverse side-effects were induced by SLS in mouth-rinses (Babich & Babich, 1997).
Amphoteric surfactant, such as cocamidopropyl betaine (CAPB) can cause significant environment deterioration. CAPB damaged the marine macroalga, Ulva lactuca. It was found that both CAPB and its metabolites are intrinsically toxic to Ulva lactuca (Vonlanthen,et al 2011).
The use of detergents in toothpastes has been reported to cause adverse effects on oral soft tissues resulting in oral mucosal desquamation, while it was reported that the detergent-free toothpaste did not result in oral desquamation. However, SLS in toothpastes significantly increased the incidence of desquamation of the oral mucosa. Both surfactants have toxicity to the oral mucosa but less toxicity was observed by CAPB detergents. It was found that Surfactant-free are safer in oral hygiene products (Herlofson & Barkvoll, 1996).
Ethanol is present in high percentage (i.e. > 25%) in many oral PCP such as mouthwashes. Several ethanol intoxication cases resulting from oral PCP ingestion were reported. A single container can supply a lethal ethanol dose to a toddler. Mouthwashes are particularly hazardous because they are thought to be innocuous, and they are widely available, attractive, and kept within easy reach of children (Weller-Fahy et al., 1980, Hornfeldt , 1992; Hoo et al., 2003, Massey & Shulman, 2006).
It was noticed that alcohol produces abnormalities in the host defenses. The increased risk of infection has been attributed to alcohol’s effect on the immune system including its effect on gut, lung and skin mucosal immunity. Ethanol seems to impair the dermal fibroblast function which plays a role in wound healing and also alcohol reduced dermal wound breaking strength (Trevejo-Nunez et al., 2015). Moreover, ethanol can directly and indirectly increase pro-inflammatory cytokine production of many cell types leading to persistent systemic inflammation and can enhance lymphocyte and keratinocyte proliferation (Farkas & Kemeny, 2013). Ethanol-treated skin cells were examined by electron microscopy. Skin cells showed organelle damage, condensed chromatin, and apoptotic bodies. Even at low concentrations, ethanol may induce apoptosis in skin cells by enhancing the effects of TNF-α (Neuman et al., 2002). Ethanol can reduce water content via a form of water loss known as transepidermal water loss, lipid content via extraction and dissolution, and protein content via denaturation. These properties allow for ethanol to be an effective (and drying) penetration enhancer. Dry skin is inherently more susceptible to issues such as a weakened epidermal barrier, which leads to less protection, can lead to inflammation, which can quicken the aging process (Wood et al., 1992; Goates & Knutson, 1994; Van der Merwe et al., 2005; Shah et al., 2008). The WHO’s International Agency for Research on Cancer (IARC) re-assessed the carcinogenicity of alcoholic beverages in the context of the IARC monographs program. ‘Ethanol in alcoholic beverages’ was classified as ‘carcinogenic to humans’ (Group 1). Overall, the IARC concluded that the occurrence of malignant tumors of the oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast is causally related to alcohol consumption. Regarding alcohol topical use, alcohol abuse has been associated with the development of several skin disorders including psoriasis, discoid eczema and superficial infections (Lachenmeier, 2008).
Triclosan (TCS) is a synthetic, broad-spectrum antibacterial agent incorporated in a wide variety of household and PCPs. The excessive use is suspected to increase the risk of emergence of TCS-resistant bacteria and the selection of resistant strains (Bedoux et al., 2012). The Food and Drug Administration banned the sale of antibacterial soaps and body washes after manufacturers failed to prove that the products’ active ingredients are safe and effective. The ban applies to products containing 19 antibacterial ingredients, including the two most common ones: triclosan, found in liquid soaps, and triclocarban, found in bar soaps. Manufacturers have to either reformulate products or remove them from the market (FDA news release, 2016).
Some synthetic fragrances have been suspected endocrine-disrupting compounds (EDCs) (i.e. compounds that can mimic the natural hormones of animals) (Pietrogrande & Basaglia., 2007).
Parabens and phthalates are potential endocrine disruptors. Parabens are suspected of having weak estrogenic and anti-androgenic activity that may increase the risk of adverse health outcomes in experimental animals, including altered gonadal hormone signaling or metabolism and spermatogenesis (Guo et al., 2014)
Thus, the EU Water Framework Directive has identified some PCPs as emerging priority candidates for monitoring and regulation. The occurrence of PCPs in municipal sewage effluent and other environmental samples could negatively impact the health of the ecosystem and the health of humans, due to persistent, long-term chronic exposure of aquatic organisms to concentrations of PCPs. (Pietrogrande & Basaglia., 2007).
SCIGATES Mouth Sanitizer
The active ingredient in SCIGATES Mouth Sanitizer is soluble capric acid. Capric acid (decanoic acid) is a medium chain fatty acid with high degree of safety and can be used as an antispetic agent. However, capric acid is water insoluble and requires high concentration to act as a good antimicrobial agent. The present SCIGATES product provides a natural foaming capric acid-silicate-arginine nanocomposite with high degree of water solubility and antimicrobial activity
References
Babich, H., & Babich, J. P. (1997). Sodium lauryl sulfate and triclosan: in vitro cytotoxicity studies with gingival cells. Toxicology letters, 91(3), 189-196.
Baker, C. L. (1931). Detergent value of sodium metasilicate. Industrial & Engineering Chemistry, 23(9), 1025-1032.
Beare-Rogers, J.; Dieffenbacher, A.; Holm, J.V. (2001). “Lexicon of lipid nutrition (IUPAC Technical Report)”. Pure and Applied Chemistry. 73 (4): 685–744
Bedoux, G., Roig, B., Thomas, O., Dupont, V., & Le Bot, B. (2012). Occurrence and toxicity of antimicrobial triclosan and by-products in the environment. Environmental Science and Pollution Research, 19(4), 1044-1065.
Bode‐Böger, S. M., Böger, R. H., Galland, A., Tsikas, D., & Frölich, J. C. (1998). L‐arginine‐induced vasodilation in healthy humans: pharmacokinetic–pharmacodynamic relationship. British journal of clinical pharmacology, 46(5), 489-497.
Creager, M. A., Gallagher, S. J., Girerd, X. J., Coleman, S. M., Dzau, V. J., & Cooke, J. P. (1992). L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. The Journal of clinical investigation, 90(4), 1248-1253.
Edwards, S. J., & Kjellerup, B. V. (2013). Applications of biofilms in bioremediation and biotransformation of persistent organic pollutants, pharmaceuticals/personal care products, and heavy metals. Applied microbiology and biotechnology, 97(23), 9909-9921.
Elmore, A. R. (2005). Final report on the safety assessment of potassium silicate, sodium metasilicate, and sodium silicate. International journal of toxicology, 24, 103-117.
Emilson, A., Lindberg, M., & Forslind, B. (1993). The temperature effect on in vitro penetration of sodium lauryl sulfate and nickel chloride through human skin. Acta dermato-venereologica, 73(3), 203-207.
Farkas, A., & Kemeny, L. (2013). Alcohol, liver, systemic inflammation and skin: a focus on patients with psoriasis. Skin pharmacology and physiology, 26(3), 119-126.
Fawzi, M, Fairfiled Melvin B. Topical antimicrobial composition, US patent 4406884, 27/09/1983
FDA issues final rule on safety and effectiveness of antibacterial soaps. Rule removes triclosan and triclocarban from over-the-counter antibacterial hand and body washes. (https://www.fda.gov/news-events/press-announcements/fda-issues-final-rule-safety-and-effectiveness-antibacterial-soaps, September 02, 2016)
Fernandes, J. D., Machado, M. C. R., & Oliveira, Z. N. P. D. (2011). Children and newborn skin care and prevention. Anais brasileiros de dermatologia, 86(1), 102-110.
Finnegan, S., & Percival, S. L. (2015). EDTA: an antimicrobial and antibiofilm agent for use in wound care. Advances in wound care, 4(7), 415-421.
Girerd, X. J., Hirsch, A. T., Cooke, J. P., Dzau, V. J., & Creager, M. A. (1990). L-arginine augments endothelium-dependent vasodilation in cholesterol-fed rabbits. Circulation Research, 67(6), 1301-1308.
Goates, C. Y., & Knutson, K. (1994). Enhanced permeation of polar compounds through human epidermis. I. Permeability and membrane structural changes in the presence of short chain alcohols. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1195(1), 169-179.
Guo, Y., Wang, L., & Kannan, K. (2014). Phthalates and parabens in personal care products from China: concentrations and human exposure. Archives of environmental contamination and toxicology, 66(1), 113-119.
Herlofson, B. B., & Barkvoll, P. (1996). Oral mucosal desquamation caused by two toothpaste detergents in an experimental model. European journal of oral sciences, 104(1), 21-26.
Hilmarsson, H., Kristmundsdottir, T., & Thormar, H. (2005). Virucidal activities of medium‐and long‐chain fatty alcohols, fatty acids and monoglycerides against herpes simplex virus types 1 and 2: comparison at different pH levels. Apmis, 113(1), 58-65.
Hoo, G. W. S., Hinds, R. L., Dinovo, E., & Renner, S. W. (2003). Fatal large-volume mouthwash ingestion in an adult: a review and the possible role of phenolic compound toxicity. Journal of Intensive Care Medicine, 18(3), 150-155.
Hornfeldt, C. S. (1992). A report of acute ethanol poisoning in a child: mouthwash versus cologne, perfume and aftershave. Journal of Toxicology: Clinical Toxicology, 30(1), 115-121.
Huang, C. B., Alimova, Y., Myers, T. M., & Ebersole, J. L. (2011). Short-and medium-chain fatty acids exhibit antimicrobial activity for oral microorganisms. Archives of oral biology, 56(7), 650-654.
Kim, N. A., Hada, S., Thapa, R., & Jeong, S. H. (2016). Arginine as a protein stabilizer and destabilizer in liquid formulations. International journal of pharmaceutics, 513(1-2), 26-37.
Kim, S. A., & Rhee, M. S. (2016). Highly enhanced bactericidal effects of medium chain fatty acids (caprylic, capric, and lauric acid) combined with edible plant essential oils (carvacrol, eugenol, β-resorcylic acid, trans-cinnamaldehyde, thymol, and vanillin) against Escherichia coli O157: H7. Food Control, 60, 447-454.
Kolderman, E., Bettampadi, D., Samarian, D., Dowd, S. E., Foxman, B., Jakubovics, N. S., & Rickard, A. H. (2015). L-arginine destabilizes oral multi-species biofilm communities developed in human saliva. PloS one, 10(5), e0121835.
Lachenmeier, D. W. (2008). Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity. Journal of Occupational Medicine and Toxicology, 3(1), 26.
Lavorgna, M., Russo, C., D’Abrosca, B., Parrella, A., & Isidori, M. (2016). Toxicity and genotoxicity of the quaternary ammonium compound benzalkonium chloride (BAC) using Daphnia magna and Ceriodaphnia dubia as model systems. Environmental Pollution, 210, 34-39.
Lee, S. I., & Kang, K. S. (2017). Function of capric acid in cyclophosphamide-induced intestinal inflammation, oxidative stress, and barrier function in pigs. Scientific reports, 7(1), 1-12.
Leung, H. W., & Paustenbach, D. J. (1990). Organic acids and bases: review of toxicological studies. American journal of industrial medicine, 18(6), 717-735.
Massey, C. C., & Shulman, J. D. (2006). Acute ethanol toxicity from ingesting mouthwash in children younger than age 6, 1989-2003. Pediatric dentistry, 28(5), 405-409.
Naito, T., Irie, H., Tsujimoto, K., Ikeda, K., Arakawa, T., & Koyama, A. H. (2009). Antiviral effect of arginine against herpes simplex virus type 1. International journal of molecular medicine, 23(4), 495-499.
Neuman, M. G., Haber, J. A., Malkiewicz, I. M., Cameron, R. G., Katz, G. G., & Shear, N. H. (2002). Ethanol signals for apoptosis in cultured skin cells. Alcohol, 26(3), 179-190.
Pietrogrande, M. C., & Basaglia, G. (2007). GC-MS analytical methods for the determination of personal-care products in water matrices. TrAC Trends in Analytical Chemistry, 26(11), 1086-1094.
Shah, D. K., Khandavilli, S., & Panchagnula, R. (2008). Alteration of skin hydration and its barrier function by vehicle and permeation enhancers: a study using TGA, FTIR, TEWL and drug permeation as markers. Methods Find Exp Clin Pharmacol, 30(7), 499-512.
Sharafudeen, R., Al-Hashim, J. M., Al-Harbi, M. O., Al-Ajwad, A. I., & Al-Waheed, A. A. (2017). Preparation and characterization of precipitated silica using sodium silicate prepared from Saudi Arabian desert sand. Silicon, 9(6), 917-922.
Thompson, Ronald. “Clitoral sensitizing arrangement using compound of menthol and L-arginine.” U.S. Patent Application 09/878,583, filed October 11, 2001.
Trevejo-Nunez, G., Kolls, J. K., & De Wit, M. (2015). Alcohol use as a risk factor in infections and healing: A clinician’s perspective. Alcohol research: current reviews, 37(2), 177.
Van der Merwe, D., & Riviere, J. E. (2005). Comparative studies on the effects of water, ethanol and water/ethanol mixtures on chemical partitioning into porcine stratum corneum and silastic membrane. Toxicology in vitro, 19(1), 69-77.
Vonlanthen, S., Brown, M. T., & Turner, A. (2011). Toxicity of the amphoteric surfactant, cocamidopropyl betaine, to the marine macroalga, Ulva lactuca. Ecotoxicology, 20(1), 202-207.
Wadaan, M. A. M., & Mubarak, M. (2009). Blood chemistry changes as an evidence of the toxic effects of anionic surfactant sodium dodecyl sulfate. Asian J. Scientific Res, 2, 113-118.
Weller-Fahy, E. R., Berger, L. R., & Troutman, W. G. (1980). Mouthwash: a source of acute ethanol intoxication. Pediatrics, 66(2), 302-305.
Wood, L. C., Jackson, S. M., Elias, P. M., Grunfeld, C., & Feingold, K. R. (1992). Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. The Journal of clinical investigation, 90(2), 482-487.
Wooley, R. E., & Jones, M. S. (1983). Action of EDTA-Tris and antimicrobial agent combinations on selected pathogenic bacteria. Veterinary microbiology, 8(3), 271-280.
Yamasaki, H., Tsujimoto, K., Koyama, A. H., Ejima, D., & Arakawa, T. (2008). Arginine facilitates inactivation of enveloped viruses. Journal of pharmaceutical sciences, 97(8), 3067-3073.
Yeo, T. W., Lampah, D. A., Gitawati, R., Tjitra, E., Kenangalem, E., Granger, D. L., … & Duffull, S. B. (2008). Safety profile of L-arginine infusion in moderately severe falciparum malaria. PloS one, 3(6), e2347.