Potential hazards due to food additives in oral hygiene products.

Food additives used to preserve flavor or to enhance the taste and appearance of foods are also available in oral hygiene products. The aim of this review is to provide information concerning food additives in oral hygiene products and their adverse effects. A great many of food additives in oral hygiene products are potential allergens and they may lead to allergic reactions such as urticaria, contact dermatitis, rhinitis, and angioedema. Dental practitioners, as well as health care providers, must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products should be explained completely to the patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for possible adverse reactions.

Introduction

Food additive term describes any substance which is not normally consumed as a food by itself and not normally used as a typical ingredient of the food, whether or not it has nutritive value, the intentional addition of which to food for a technological (including organoleptic) purpose in the manufacture, processing, preparation, treatment, packing, packaging, transport or holding of such food results, or may be reasonably expected to result, (directly or indirectly) in it or its by-products becoming a component of or otherwise affecting the characteristics of such foods (1). This term does not include “contaminants” or substances added to food for maintaining or increasing nutritional quality (1, 2). Food additives used to preserve flavor or enhance the taste and appearance of foods are also available in dental materials (2,3,4,5,6).

The mouth is subjected to a wide spectrum of antigenic agents, including foodstuffs and drugs, cosmetics, metals in eating utensils, dental materials together with toothpastes and filling materials, and microorganisms. Hypersensitivity to such antigens may manifest in a number of diverse ways, including angioedema and ulceration or lichenoid reactions (7). Patients undergoing dental treatment can be exposed to many potential allergens, but adverse events are infrequent. Patients with symptoms or signs of stomatitis, burning, tingling, cheilitis, oral lichenoid lesions, lip and facial swelling may relate these problems to dental treatment or to the use of dental products. Gawkrodger (2), reported patients with oral mucosal diseases are more likely to have demonstrable hypersensitivity to food additives, especially benzoic acid, perfumes and flavorings, especially cinnamaldehyde. Cheilitis is an inflammatory eruption on the lip which can have several causes. Some food additives reported to cause cheilitis such as potassium persulphate in denture cleansers, castor oil in chewing gum and colophonium in dental floss (3,4,5,6).

The aim of this review is to provide information concerning food additives in oral hygiene products along with their reported adverse effects.

Food Labelling and E Numbers

The International Codex Alimentarius Commission (Codex Alimantarius Comission-CAC) was established by collaborative working of The World Health Organization (WHO) and the Food and Agriculture Organization (Food and Agriculture Organization-FAO) (1, 8). Categories of food additives are indicated according to purpose of their usage and following special names, “E” numbers on prepared food packages. Classification of food additives according to basic functions are; Colours (E100-180), Preservatives (E200-297), Antioxidants (E300-321), Emulsifiers and Stabilizers (E322-500), Acidity Regulators (E500-578), Sweeteners and Provider Odor (E620-637), Wide purpose (E900- 927) (9).

Food Additives in Oral Hygiene Products Toothpastes

Toothpastes are presented in different concentrations of fluoride and special versions present natural components (e.g. propolis and jua), for specific functions, (e.g.tooth bleaching, dental erosion control or to reduce sensitivity) (10). Ingredients used in modern toothpaste formulations include abrasive agents, tensoactives, humectants, thickening agents, flavoring, coloring agents and antimicrobial agents (11). Abrasives represent a minimum of 50% of a typical toothpaste. Representative abrasives include calcium carbonate, dehydrated silica gels, hydrated aluminum oxides, magnesium carbonate, phosphate salts and silicates to remove debris and residual surface stains. Fluoride in various forms is the preferred active ingredient in toothpaste to prevent dental caries. Several toothpastes contain sodium lauryl sulfate (SLS) or related surfactants (detergents). Antibacterial agents, such as Triclosan or zinc chloride prevent gingivitis, helps reduce tartar and bad breath. Toothpastes have different colors, and flavors intended to encourage use of the product. Three commonest flavorants are peppermint,spearmint, and wintergreen. Humectants to prevent water loss within the dentifrice include glycerol, propylene, glycol and sorbitol. Thickening agents or binders to stabilize the toothpaste formula include mineral colloids, natural gums, seaweed colloids or synthetic cellulose (11, 12). Hydroxyapatite nanocrystals and a variety of calcium phosphates are included in toothpaste formulations for remineralization (13).

Reports have suggested triclosan, an active ingredient in several toothpastes, can combine with chlorine in tap water to make chloroform, that the United States Environmental Protection Agency classifies as a probable human carcinogen (14). Lawrence et al. (15) reported an eleven-year old patient with multiple, asymptomatic ulcerated lesions located in the oral cavity associated with triclosan found within the patient’s dentifrice. Abdollahi et al. (16) reported that dentifrice hypersensitivity reactions seem to be more common since the advent of tartarcontrol toothpastes. Kowitz et al. (17) evaluated four completely different toothpastes in ninety two dental students and dental hygiene students. They reported increased rates of mucosa reactions (e.g. ulceration, sloughing, erythema, etc.) with tartarcontrol toothpastes. Flavorings in toothpastes provide the ‘fresh clean taste’ and mask the bitter taste of pyrophosphates in tartar-control toothpastes (11). According to a multicenter study of allergic contact cheilitis from toothpaste, flavoring agents especially derivatives extracted from the main varieties of mint (such as spearmint, peppermint, menthol, and carvone) were the most related agents with allergic contact cheilitis (18). Case reports of plasma cell gingivitis have been reported with the use of herbal toothpaste containing cinnamon (19). Cinnamonaldehyde, which is usually added to dentifrices to cover the unpleasant taste of pyrophosphate, has been related to the development of plasma cell gingivitis (19, 20). Miller et al. (21) represented fourteen cases of cinnamon induced stomatitis.

The effectiveness of toothpastes significantly increases by the addition of surface-active agents. These surface-active materials not solely provide the effervescent action of dentifrices and enhance the removal of food particles, but they also help within the distribution of the toothpaste in the oral cavity (22). Sodium lauryl sulphate (SLS) and sodium lauryl sarcosinate are the two most common surfaceactive agents (23). Industrially, SLS is used in hard surface cleansing products, grease cleaners, car washing and detergents, personal hygiene products (e.g. shampoos and shower gels, bath foams, face cleansing soaps), and toothpastes as detergents and foaming agents. The frequent use of this material may lead to multiple allergic and toxic reactions (6, 24,25, 26,27,28). Ersoy et al. (29) reported a case with abdominal gas, cramps, bloatedness and diarrhea complaints due to SLS in patient’s toothpaste. Researchers have concluded that the local application of toothpastes containing SLS may cause oral lesions due to absorption of the material sublingually or from the oral mucosa (6, 23, 27, 29). Hypersensitivity reaction to toothpastes is rare. Some flavor and color additives used in toothpastes may cause allergic reactions such as scaling on lips and tongue, edema, perioral dermatitis, angular chelitis, gingivitis and intraoral ulcers. These symptoms appear within a few minutes after using toothpaste (30).

Mouthwashes

Mouthwash is defined as a non sterile solution used principally for its deodorant, refreshing or antiseptic effect and also they are designed to remove food particles, temporarily reduce halitosis and offer a pleasant taste (31). Ingredients of mouthwashes are determined by American Dental Association (ADA) as follows: basic ingredients include water, alcohol, cleansing agents, flavoring ingredients and coloring agents. Active ingredients vary depending on the type of mouthrinse, however they can be placed into four general groups: First group include antimicrobial agents which act directly on oral microorganism to help reduce plaque, decrease the severity of gingivitis and control bad breath. Second group includes fluoride which helps reduce tooth decay and make teeth more resistant to caries. Third group includes astringent salts which can serve as temporary deodorizers that mask bad breath. Finally, fourth group includes the odor neutralizers which act by chemically inactivating odor causing compounds (12).

The Food and Drug Administration (FDA) classifies mouthrinses as either cosmetic or therapeutic, or a mixture of the two. The cosmetic mouthrinses are over the counter products that are mainly intended as mouth fresheners. Therapeutic mouthrinses can be sold as prescription or over the counter products that have an additional active ingredient and are marketed as antiplaque/antigingivitis and anticaries drug products (32). The localized oral lesions induced by mouthrinses include lesions of the primary irritant type and lesions generated through activation of specific immunologic pathways such as type I and type IV hypersensitivity reactions (33,34,35,36). Kowitzet al.(37) have reported the irritating effect of mouthwashes to the oral mucosa by demonstrating the occurrence of epithelial peeling, mucosal ulceration and inflammation, gingivitis, and petechiae in twenty fifth of 104 dental and dental hygiene students who used 20 ml of a mouthwash for five seconds, twice daily, during a 2-week period. The reported symptoms disappeared completely when use of the mouthwashes was interrupted. In a susceptible host, mouthwashes have also been shown to produce hypersensitive reactions, triggered by a range of ingredients. Hypersensitive reactions triggered by mouthrinses have been reported in the literature (38,39,40). Mathias et al.(39) reported a case of contact urticaria that developed after use of a cinnamic aldehyde-containing mouthwash in which lip swelling occurred. Lim et al.(38) reported perioral and mucosal edema caused by contact allergy to proflavine (an antiseptic) in an acriflavine (a proflavine derivative) mouthwash. In another case report, benzydamine mouthwash use was shown to provoke a maculopapular rash on the trunk and limbs of a patient (40).

Chlorhexidine (CHL) is a synthetic topical disinfectant. It is usually insoluble in water thus it has to be formulated with either gluconic or acetic acid to create watersoluble digluconate or diacetate salts. Chlorhexidine, especially as digluconate ester, is widely used in various topical applications (mouthwash solutions, dental gels and toothpaste) for its capability to bind oral mucosal surfaces inhibiting plaque formation (41). The adverse effects of chlorhexidine are reported as altered taste sensation, superficial desquamation of the oral mucosa, brownish discoloration of the tongue and teeth, increased calculus formation and stomach upsets (42). Rare reports are published about cutaneuos adverse reactions following the use of CHL in mouth-wash rinses resembling fixed drug eruption or contact stomatitis, urticaria and anaphylaxis are reported after the use of CHL mouth-wash rinses (34, 35, 43,44,45,46). The patients in many reported cases later tested positive for chlorhexidine induced hypersensitivity reaction by means of intradermal, scratch, and epicutaneous tests (43, 45, 47, 48). Practitioners should be aware of the potential for both minor and serious adverse side effects of CHL.

Ethanol is contained in a number of ready-to-use mouthwashes in a concentration generally between 5% - 27% volume (49, 50). However, ethanol itself is not thought to have a direct carcinogenic effect on the oral mucosa. Acetaldehyde, the primary metabolite of ethanol is known to be a mutagenic and carcinogenic agent, and is assumed to play the main role in carcinogenesis (51). Mouthwashes with a high alcohol content have been shown to produce hyperkeratotic lesions in both human and animal models (52). Bemstein (33) reported two cases of oral mucosal white lesions associated with Listerine mouthwash. There is limited and conflicting epidemiological evidence on the link between the use of ethanol in the oral cavity within the form of mouthwashes and oral cancer. Some studies pointed to an increased risk of oral cancer due to locally produced acetaldehyde, operating via the same mechanism to that found after alcoholic beverage ingestion (53, 54). A review article by McCullough and Farah (54) concluded that there is sufficient evidence to accept the proposition that developing oral cancer is increased or contributed to by the use of alcohol-containing mouthrinsees. Lachenmeier et al. (53) investigated acetaldehyde levels in saliva after use of alcohol-containing mouthwashes. They reported a twice-daily use of alcohol-containing mouthwashes leads to a systemic acetaldehyde exposure of 0.26 lg/kg bodyweight/day on average, that corresponds to a lifetime cancer risk of 3E-6. Reidy et al.(51) reviewed the literature on the effects of alcohol on the oral mucosa.

They conluded the evidence concerning the carcinogenic effect of alcohol-containing mouthrinses is conflicting, and also the relationship between alcohol-containing mouthrinses and oral cancer has not yet been firmly established. Two meta-analysis on the relationship between alcohol-containing mouthrinses and oral cancer by La Vecchia (55) and Gandini et al. (56) concluded that a link between mouthrinse use, specifically alcohol-containing mouthrinses, and oral cancer is not supported by epidemiological evidence. Reviews by Cole et al. (57) and Elmore and Horowitz (58) also concluded that the available epidemiological evidence failed to support a link between alcoholcontaining mouthrinse use and oral cancer. It has been demonstrated that alcohol-free oral rinses are as effective as their alcohol-containing counterparts, and so the need for ethanol in mouthwashes and oral rinses seems to be non-existent (59,60,61). Products without alcohol have also been shown to have a lower incidence of other adverse effects (62). The use of alcohol-containing mouthrinses should be limited to short-term therapeutic situations for a limited and controlled period of time.

Chewing Gum

Chewing Gum removes plaque and food debris on the teeth, stimulates the flow of saliva, raises of plaque pH, encourages remineralisation, stops demineralisation, reduces gingivitis, but may have adverse effects on TMJ (63,64,65). Chewing gum consists of a gum base, sweetener, flavoring and aromatic agent. Gum base consists a combination of elastomers, naturel or/and synthetic resins, oils, emulsifiers, waxes, antioxidants and fillers (66, 67). Sweetener is defined by Codex Alimentarius Commission as “which give sweet taste to food but which is not sugar”. Sweeteners have shown completely different physical, chemical, physicochemical structures as they have different chemical structures. “Sugar-Free” label is only given to sugar alcohols, artificial sweeteners and mixtures of them by FDA (68). Most chewing gums sold are sweetened with sugar substitutes (69). Sugar substitutes are food additives that duplicate the taste of sugar in food, however don’t supply food energy or calories. Some sugar substitutes are natural and others are synthetically produced. These synthetically produced sweeteners are usually called artificial sweeteners (70). The predominant sugar substitutes are polyols, which are low-caloric substances sometimes referred to as ‘sugar alcohols’ because their chemical structure is similar to that of both sugar and alcohol.

The most common polyols in sugar-free chewing gum are sorbitol, which is a hexatol derived from glucose, and xylitol, which is a pentatol that occurs widely in nature (69, 71). Substances which do not give calories or do not increase blood sugar and tastes sweet are called “artificial sweeteners”. The main artificial sweeteners are; Aspartame, Acesulfame K, Saccharin, Sucralose, and Cyclamate (72). Xylitol is entirely natural and added to pastilles, chewing gums, toothpastes and mouthwashes as a ‘tooth friendly’ component (73). Consumption of large amounts of polyols have laxative effect. They may cause bloating, intestinal gas and diarrhea (72). Polyol-based sugarfree products may decrease caries incidence however they may bring another dental health risk, dental erosion, if they contain acidic flavoring (74).

Clinicians may consider recommending xylitol use to moderate or high caries-risk patients. The changes in caries risk status must be checked and also the frequency of xylitol use and recommendations must be adjusted accordingly (75). Although frequent consumption of food additives, advers reactions related to these substances are more rare in general population (0.01%-0.23%) while more common in atopic people (2%-7%). Reported reactions are mostly mild and they can have an effect on digestive or respiratory tracts, skin and they can rarely cause anaphylaxis (76). There is very little information regarding side effects of food additives on oro-dental health. While an undisturbed oral mucosa with normal salivation is characterized by a certain resistance and regeneration ability, decreased saliva production, microbial mucosal colonization, mechanical trauma and long-term exposure to irritation and allergen like substances disrupt its barrier function and create conditions for the development of a delayed hypersensitivity (77). The oral cavity, including the lips, is consistently exposed to a large number of potentially irritating and sensitizing substances. Dental materials, oral hygiene products and food additives may cause contact allergic reactions in the mouth with varied clinical presentation. Oral lichenoid lesions may be evoked by hypersensitivity to dental restorative metals, acrylates, flavorings and other substances (78). The clinical manifestations of contact hypersensitivity in the mouth vary from subjective difficulties like burning, pain and dryness of the mucosa (burning mouth syndrome) to objective changes within the form of nonspecific stomatitis and cheilitis with reddish, edematous mucosae, erosions and ulcers (1, 79, 80).

These chronic changes are most frequently related to long-term exposure of the oral mucosa to dental metals, and additionally to acrylates, composite materials, additives and other substances, that cause the development of a delayed hypersensitivity reaction (81, 82). The cause of an immediate (type I) reaction (contact urticaria) is identified by skin prick/scratch testing (83). Skin prick testing provides information about the presence of specific IgE to protein and peptide antigens (allergens).However, the low concentration of the allergen in a product may be too low to give a positive reaction. As in all forms of contact allergy, the best treatment is avoidance of the product and allergen if identified (84).Due to the premalignant character of oral lichenoid lesions, epicutaneous tests to verify suspect intraoral allergens and follow up of these patients are important. Cooperation with dentists is necessary for the correct identification of potential allergens in the used dental materials. The replacement of suspect dental materials and other substances must be performed (78). When educating patients on oral health, dental professionals need to not solely discuss the benefits of oral hygiene products but also potential side effects; recommended frequency of use; and proper dosage levels. Recommendations of delivery or product type should be given to patients on a case-by-case basis, taking into consideration age, dental health status, systemic health considerations, and patient preference (75).

Conclusion

Dental practitioners as well as health care providers must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products must be explained completely to patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for adverse reactions.