Table 1.

Study characteristics of included studies

Category	Type of study	In vitro/ In vivo	SLS exposure	Outcome	References
Effects on free fluoride concentration in oral fluids	RCT	In vivo (human)	48 h massed plaque, before washing with a 12 mmole/l NaF (228 μg/g F rinse) mouthwash with 0.5% SLS or without 0.5% SLS	SLS had small effect on total plaque fluoride. SLS made a small non-significant increase in total saliva fluid. SLS significantly increased plaque fluid and salivary fluid fluoride	[ 1 ]
Wound Healing	Experimental	In vitro	HGFs cultures took one of the SLS order: from 0.00% (control), to 0.05% SLS (w/v) (with 0.01 interval between group) in media containing 5% FBS, for 2 minutes. Cultures termination on days 0, 2, 4, 6 and 8	SLS significantly inhibited wound healing	[ 2 ]
Impact on e-tongue device	Experimental	In vitro	Solution with 1% SLS tested on electronic tongue.	SLS changes the “test” signal sensor sets in compared to control sensor.	[ 3 ]
				The performance of the sensor was not harmed by this change
Management of halitosis	Experimental	In vivo	0.005-5% SLS + cell-free FTF enzyme and fructans	FTF activity and ECPs structure changes decreased	[ 4 ]
Management of halitosis	RCT	In vivo (human)	SLS (0 %, 1.1 %, 2.2%) in detergent	Sulfide gas decreased significantly ammonia decreased but not significantly	[ 5 ]
Plaque index	RCT	In vivo (human)	toothpastes (0%, 1.1% and 2.2% SLS) for 4 weeks.	increased SLS concentration is associated with decreased plaque control and Salivary flow but not significantly	[ 6 ]
Cytotoxicity	Experimental	In vitro	2% SLS + cementum for 1, 3 and 5 minutes.	SLS can remove the root surface completely and partially dependent to exposure of time.	[ 7 ]
Solubilizer	RCT	In vivo (human)	1-5% SLS and non-SLS toothpaste for 8 weeks	SLS and non-SLS toothpastes showed same efficacy nevertheless containing one seems more pleasant for patients	[ 8 ]
Effects on saliva	RCT	In vivo (human)	1% SLS only, 4% betaine only, 1% SLS- 4% betaine containing and control toothpastes for 6 weeks	Other ingredients of toothpastes might be more responsible for mucosal irritating effects rather than SLS	[ 9 ]
EC	Case-report	In vivo (human)	SLS containing toothpaste	SLS might be a responsible element EC	[ 10 ]
Recurrent aphthous stomatitis	Crossover RCT	In vivo (human)	Usual brushing method + dentifrice and toothbrush supplied. Three dentifrices	SLS-containing toothpastes affected the ulcer healing process and it was significantly lower in SLS-free group.	[ 11 ]
			1. A commercially available SLS-free dentifrice
			2. A dentifrice containing 1.5% SLS	Patients from these group reported more pain in daily lives
			3. A commercially available 1.5% SLS-containing dentifrice
Recurrent aphthous stomatitis	Systematic review	In vivo (human)	4 crossover clinical trials: systematic review meta-analysis: 2 clinical trials	SLS‐free dentifrice significantly reduced the ulcers’ number, ulcer duration, episodes’ number, and ulcer pain compared to SLS‐containing	[ 12 ]
Carrier for various oral drugs	RCT	In vivo (rat)	Dissolved in water, 2% solution	Significant only in ileum	[ 13 ]
Carrier for various oral drugs	Experimental	In vitro	0.5% w/v SLS in water	The CMC of SLS:	[ 14 ]
				water> FeSSIF> SGF
				aggregation of SLS:
				SGF>FeSSIF>water
				Optimum solubility happened when 2 mg of SLS was used.
Carrier for various oral drugs	Experimental	In vitro	Anionic form SLS Water based solution	SLS has no - effect on e-tongue sensors	[ 3 ]
Carrier for various oral drugs	Experimental	In vitro	2:1 SLS : mirabegron Salt	SLS reduced solubility of the drug and slows down drug release, for it has sulfate and alkyl groups	[ 15 ]
Carrier for various oral drugs	Experimental	In vitro	Dried form and Suspension form of SLS salt/complex and microparticles containing SLS salt/complex	The microparticles have slower dissolution profiles than LS salt/ complex. There were no significant differences between dissolution profiles of suspensions and dried forms of salt/complex and microparticles containing LS salt/complex	[ 16 ]
Carrier for various oral drugs	RCT	In vivo (rats)	3 groups Mirabegron alone as solution (1.25mg/mL), SLS/drug suspension, SLS/drug microparticles suspension	The microparticle suspension showed a better performance in dogs than LS salt/complex suspension. In mirabegron alone group, maximum concentration of the drug in plasma was higher in the fasting group that could get rapidly toxic. Using a suspension, the difference between fasting and fed groups was decreased.	[ 16 ]
				Microparticle suspension produced similar results under fasted and fed conditions.
Carrier for various oral drugs	Experimental	In vitro	19 drugs (Acetaminophen, Benzoic Acid, Budesonide, Carbamazepine, Carvedilol, Celecoxib, Enrofloxacin, Glibenclamide, Ibuprofen, Indomethacin, Ketoconazole, Lamotrigine, Mycophenolate, mofetil, Phenothiazine, Naproxen, Phenytoin, Piroxicam, Salicylic Acid, Tadalafil)+SLS (0.5% & 0.1%)	The solubility of most drugs increased (different among drugs, Acetaminophen the least & Ketoconazole the most)	[ 17 ]
Carrier for various oral drugs	Experimental	In vitro	150 mg BILR355+ SLS & PVP (1:1 w/w), SLS +excess API in 7 mL water + 0.01% to 1.0% (w/v) or (0.35 to 34.7 mM)	SLS spectrum > Cognis for BILR 355 dissolution but both were good.	[ 8 ]
Carrier for various oral drugs	Experimental	In vitro	pre-dissolved HPMC-AS or SLS (0.3, 1, or 3 mg/mL) + (1 & 3 mg/ml HMPC-AS), LLPS (amorphous precipitates)	SLS increased PSZ solubility+ synergism with HMPC, SLS (3 mg/ml) reduced the precipitation of PSZ & crystallization inhibition not useful for in vivo LLPS increased drug bioavailability	[ 18 ]
Carrier for various oral drugs	Experimental	In vivo (rats)	A nanosuspension for Isradipine containing: SLS + vitamin E + TPGS (particle size = 539 nm)	The particle size reduction can influence ISR absorption in gastrointestinal tract and thus nanosuspension technology is responsible for the increase of oral bioavailability in rats.	[ 19 ]
Carrier for various oral drugs	Experimental	In vitro	SLS as an oral mucosal penetration enhancer for Pravastatin Sodium tablets	Muco-adhesive layered buccal tablets containing 1% SLS produced a good mucoadhesive strength, 96% drug release over 2 h, and 23% permeation of the drug through buccal mucosa without any tissue damage.	[ 20 ]
Carrier for various oral drugs	RCT	In vivo (human)	Accumulated plaque for 48 h before rinsing with a 12 mmole/l NaF (228 μg/g F) rinse containing or not containing 0.5% (w/w) SLS	SLS had no statistically significant effect on total plaque and total saliva fluoride but significantly increased salivary fluid and plaque fluid fluoride.	[ 1 ]
Cytotoxicity	experimental	In vitro	Toothpaste and mouthwash	SLS should be replaced with safer detergents	[ 21 ]
Cytotoxicity	experimental	In vivo (rabbit, rat)	Gel SLS (2%, w/w)vaginal, Rectal and Penile mucosaEye, Skin, Buccal mucosa	gel formulation containing the 2%ww of SLS, can be considered safe for the buccal mucosa.	[ 22 ]
Enamel erosion	experimental	In vitro	SLS Solution with concentrations of 1.0 and 1.5%	The protection of fluoride decreased in the initial erosion, but this effect did not remain with the preservation of the erosive cycle.	[ 19 ]
Mucosal reactions	Case-report	In vivo (human)	Toothpaste containing SLS	oral lesions	[ 23 ]
Mucosal reactions	Case-report	In vivo (human)	Toothpaste containing SLS	oral mucosal desquamation	[ 24 ]
Mucosal reactions	Case-report	In vivo (human)	Toothpaste containing SLS	allergy	[ 56 ]
Mucosal reactions	triple case-report	In vivo (human)	Toothpaste containing SLS	inflammatory reactions of the anterior dorsal tongue	[ 26 ]
Mucosal reactions	experimental	In vivo (rats)	oral mucosa	Contact sensitivity-like reactions were found .in the oral mucosa	[ 27 ]
Mucosal reactions	crossover RCT	In vivo	The toothpastes with 1.2% SLS, 1.2% SLS + 4% betaine and only with 4% betaine were placed on buccal mucosa for 15 min	SLS: irritates the oral mucosa Betaine: does not reduce the effect of SLS	[ 28 ]
Mucosal reactions	experimental	In vitro	human oral mucosa cultures + SLS 0%, 0.015%, 0.15%, 0.5%, 1.0% and 1.5%	SLS can have a dual effect on the human oral epithelium	[ 29 ]
Interactions with CHX	RCT	Human	Regimen A (positive control): rinsing with CHX alone.	No significant difference in bleeding index.	[ 30 ]
			Regimen B: rinsing with CHX preceded by rinsing with an SLS-containing slurry Regimen C: rinsing with CHX preceded by tooth brushing with an SLS-containing dentifrice	Regimen B showed statistically significant higher plaque accumulation.
Interactions with CHX	Meta-Analysis	-	4 RCTs were included:	the combined use of dentifrice and CHX mouthwash is not contraindicated.	[ 31 ]
			Comparing CHX mouthwash as a single oral hygiene intervention with the use of CHX in combination with SLS-free and with SLS-containing dentifrices	Moderate risk of bias was detected.
Other	Experimental	In vitro	Adhesive (0.5% and 0.6%)+ SLS (concentration range 0.0025%-0.0075%)	The cell death was dominated by necrosis, but apoptosis was increased with SLS concentrations and was the prevailing death mechanism at SLS concentrations of 0.0075%	[ 32 ]
Other	Experimental	In vitro	commercially available toothpastes containing SLS	Detergents’ type in toothpastes associated with changes in in-vitro cell toxicity	[ 33 ]
Other	RCT	In vivo (human)	SLS detergents 2.0% w/v with and without 4.0% w/v betaine in distilled water in 20 volunteers, and 0.5% and 1.0% w/v SLS combined with 4.0% w/v betaine	Betaine was ineffective on the immediate mucosal impact of 0.5% and 2% SLS or 2% CAPB, but abolished the irritating effect of 1% SLS.	[ 28 ]
Other	RCT	In vivo (human)	The ability of Ndu tea® and Lipton® tea containing 1.2% w/v SLS	The extracts of Ndu and Lipton tea potently reduced the CFU/milliliter by SLS	[ 34 ]

RCT: Randomized clinical trial, HGFs: Human gingival fibroblasts, FTF: Fructosyltransferase, EC: Exfoliative cheilitis, W/V: Weight/Volume

CMC: critical micelle concentration, SGF: simulated gastric fluid, FeSSIF: Fed state simulated intestinal fluid, ISR: Isradipine, PVP: Polyvinyl pyrrolidone

LDAO: lauryldimethylamine N-oxide, API: Active pharmaceutical ingredient, HMPC: Hydroxy propyl methyl cellulose acetate succinate

LLPS: liquid-liquid phase separation, PSZ: Posaconazole, VPS: Vinylpolysiloxane, CAPB: Cocamidopropyl betaine, CFU: Colony Forming Unit

CHX: Chlorhexidine