Repeated-dose toxicity and toxicokinetic study of isobutylparaben in rats subcutaneously treated for 13 weeks.

Parabens have historically served as antimicrobial preservatives in a range of consumables such as food, beverages, medications, and personal care products due to their broad-spectrum antibacterial and antifungal properties. Traditionally, these compounds were believed to exhibit low toxicity, causing minimal irritation, and possessing limited sensitization potential. However, recent evidence suggests that parabens might function as endocrine-disrupting chemicals (EDCs). Consequently, extensive research is underway to elucidate potential human health implications arising from exposure to these substances. Among these parabens, particular concerns have been raised regarding the potential adverse effects of iso-butylparaben (IBP). Studies have specifically highlighted its potential for inducing hormonal disruption, significant ocular damage, and allergic skin reactions. This study aimed to evaluate the prolonged systemic toxicity, semen quality, and estrus cycle in relation to endocrine disruption endpoints, alongside assessing the toxicokinetic behavior of IBP in Sprague-Dawley rats following a 13-week repeated subcutaneous administration. The rats were administered either the vehicle (4% Tween 80) or IBP at dosage levels of 2, 10, and 50 mg/kg/day for 13 weeks. Blood collection for toxicokinetic study was conducted on three specified days: day 1 (1st), day 30 (2nd), and day 91 (3rd). Systemic toxicity assessment and potential endocrine effects were based on various parameters including mortality rates, clinical signs, body weights, food and water consumption, ophthalmological findings, urinalysis, hematological and clinical biochemistry tests, organ weights, necropsy and histopathological findings, estrus cycle regularity, semen quality, and toxicokinetic behavior. The findings revealed that IBP induced local irritation at the injection site in males at doses ≥ 10 mg/kg/day and in females at 50 mg/kg/day; however, systemic toxicity was not observed. Consequently, the no-observed-adverse-effect level (NOAEL) for IBP was determined to be 50 mg/kg/day in rats of both sexes, indicating no impact on the endocrine system. The toxicokinetics of IBP exhibited dose-dependent systemic exposure, reaching a maximum dose of 50 mg/kg/day, and repeated administration over 13 weeks showed no signs of accumulation.

Placental transport of parabens studied using an ex-vivo human perfusion model.

INTRODUCTION: Parabens are a group of chemicals widely used as preservatives in daily consumer products such as cosmetics, food items, pharmaceuticals and household commodities. They have been broadly detected in human samples indicating a general human exposure, and concerns arose from their potential endocrine disrupting effect. Especially the exposure to parabens during pregnancy is concerning, as the time of fetal development is a particularly vulnerable period. The aim of this study was to investigate the transport and metabolism of four commonly used parabens: methyl-, ethyl-, propyl- and butylparaben (MeP, EtP, PrP and BuP) and the metabolite para-hydroxybenzoic acid (PHBA) across the human placenta. METHODS: An ex-vivo human placental perfusion model was used. The test compounds were added in the maternal compartment (with initial concentrations of 1 mM or 0.1 mM). Placental transport was evaluated by fetal-maternal concentration ratios (FM-ratio), transport index (TI) and indicative permeability (IP). RESULTS: Information about parabens kinetics was taken from 10 perfusions and PHBA from 7 perfusions. Paraben metabolism was not detected. The placental transport of MeP, EtP, PrP, BuP and PHBA revealed a transfer from maternal to fetal circulations with FM120 of 0.86 ± 0.27 (MeP), 0.98 ± 0.28 (EtP), 1.00 ± 0.28 (PrP), 1.12 ± 0.59 (BuP) and 0.82 ± 0.37 (PHBA). The test substances accumulated in the perfused tissue in some degree. The average kinetic parameters FM-ratio, TI and IP were not different between chemicals. DISCUSSION: The present study shows that the placenta barrier is permeable to all four parabens and the metabolite, which implies potential fetal exposure.

Amended Safety Assessment of Methylchloroisothiazolinone and Methylisothiazolinone as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reassessed the safety of the mixture Methylchloroisothiazolinone (MCI)/Methylisothiazolinone (MI), which functions as a preservative in cosmetic products. The Panel reviewed relevant animal and human data provided in this safety assessment, and data from the previously published safety assessment of this mixture, and concluded that MCI/MI is safe in cosmetics when formulated to be nonsensitizing, based on the results of a quantitative risk assessment or similar methodology; however, at no point should concentrations exceed 7.5 ppm in leave-on products or 15 ppm in rinse-off products.

Amended Safety Assessment of Methylisothiazolinone as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reassessed the safety of Methylisothiazolinone, which functions as a preservative in cosmetics. The Panel reviewed relevant animal and human data provided in this safety assessment, and data from the previously published safety assessments of Methylisothiazolinone, and concluded that Methylisothiazolinone is safe for use in rinse-off cosmetic products at concentrations up to 100 ppm (ie, 0.01%) and safe in leave-on cosmetic products when they are formulated to be nonsensitizing, which may be determined based on a quantitative risk assessment or similar methodology.

In vitro skin penetration of bronidox, bronopol and formaldehyde from cosmetics.

The objective was to evaluate the influence of the formulation in the in vitro transdermal absorption through pig ear skin of three preservatives, bronopol, bronidox and formaldehyde as well as the absorption of formaldehyde from bronopol and dimethyloldimethyl hydantoin (DMDM hydantoin). An aqueous solution, an O/W emulsion and a hydrogel were assayed. Bronidox and bronopol absorption depends on the formulation. The O/W emulsion was the system that least promoted absorption of bronidox while the absorption of bronopol was lower from the hydrogel. The aqueous solution provided maximal transdermal absorption of both preservatives. Moreover, the transdermal absorption of formaldehyde released from bronopol also depends on the formulation, being the aqueous solution the system that allowed greater absorption. Transdermal absorption of formaldehyde, applied directly or released from DMDM hydantoin, is not conditioned by the excipients. The degree of transdermal absorption of all the preservatives tested is low and therefore the concentrations allowed by regulations are safely used. Nonetheless, since formaldehyde was detected in the receptor compartment after a long time exposure to bronopol and DMDM hydantoin it would be important to consider the possibility of limiting the use of these two preservatives to rinse off products as is the case of bronidox.

Distribution of benzalkonium chloride into the aqueous phases of submicron dispersed systems: emulsions, aqueous lecithin dispersion and nanospheres.

Partitioning of benzalkonium chloride (BAC) into the aqueous phases of submicron dispersed systems such as submicron emulsions, aqueous lecithin dispersion (WLD), and suspension of nanospheres (NLC) was studied. The aqueous phases of the investigated systems were obtained by ultracentrifugation and subsequently were subjected to ultrafiltration, which procedure allowed distinguishing between the fractions of free benzalkonium chloride (w) and those incorporated in the liposomal and micellar region (wlm). The fractions present in the oily phase and in the interphase of submicron emulsions were calculated. Despite the various composition of the investigated formulations and the initial concentration of BAC, w values were very small at 0.2-8.0%. The wlm value in submicron emulsions was increased by increasing the total concentration of preservative from 29.0 to 42.0%. Using polysorbate 80 instead of lecithin resulted in a distribution of BAC to aqueous-liposomal-micellar phase that was twice as high. The very low concentration of antimicrobial active form of benzalkonium chloride was analyzed in the aqueous phase of emulsions stabilized with lecithin as well as in aqueous lecithin dispersion and nanospheres (below 3%). Replacement of lecithin with polysorbate 80 in emulsions with polysorbate significantly increase (up to 8%) the fraction of benzalkonium chloride in the aqueous phase where microbial growth occurs.

Safety review of phenoxyethanol when used as a preservative in cosmetics.

Phenoxyethanol, or 2-phenoxyethanol, has a large spectrum of antimicrobial activity and has been widely used as a preservative in cosmetic products for decades. It is effective against various Gram-negative and Gram-positive bacteria, as well as against yeasts, and has only a weak inhibitory effect on resident skin flora. According to the European Scientific Committee on Consumer Safety, phenoxyethanol is safe for all consumers - including children of all ages - when used as a preservative in cosmetic products at a maximum concentration of 1%. Adverse systemic effects have been observed in toxicological studies on animals but only when the levels of exposure were many magnitudes higher (around 200-fold higher) than those to which consumers are exposed when using phenoxyethanol-containing cosmetic products. Despite its widespread use in cosmetic products, phenoxyethanol is a rare sensitizer. It can be considered as one of the most well-tolerated preservatives used in cosmetic products.

Pharmacokinetic profile of propyl paraben in humans after oral administration.

Parabens are commonly used as antimicrobial preservatives in consumer products. Because of their possible endocrine-disrupting activities, their safety has become a public concern. Although pharmacokinetic studies on parabens have been conducted in animals, limited information exists on their pharmacokinetic profiles in humans. In the present study, we determined the pharmacokinetic characteristics of propyl paraben (PP) in humans following a single oral administration of 0.6 mg/kg bw of deuterium labeled-PP. We also conducted experiment with similar design but different exposure amount (2.5 mg/kg bw) to verify the validity of the model to be developed. Blood and urine were collected at several intervals over the course of 48 h to measure levels of PP and its metabolites (conjugates and hydrolysates) in 12 male volunteers. The unconjugated parent compound (free PP), glucuronide and sulfate conjugates, p-hydroxybenzoic acid, and p-hydroxyhippuric acid were measured using HPLC-MS/MS. It was found that PP was rapidly absorbed via ingestion within 2 h and quickly eliminated (terminal half-life, 2.9 h). The fraction of administered dose excreted in the urine was 0.05% for free PP, 8.6% for total PP (free + conjugates), 23.2% for p-hydroxyhippuric acid, and 7.0% for p-hydroxybenzoic acid. Utilizing this pharmacokinetic profile, we successfully constructed a multi-compartment model where the disposition of PP was well described with two compartments and that of its metabolites was explained with first-order reactions. The present pharmacokinetic model provides insights into the kinetic properties of the disposition of PP and its metabolites in humans, and it can be used for risk assessment with biomonitoring of PP.

Percutaneous permeability of 1-phenoxy-2-propanol, a preservative in cosmetics.

1-Phenoxy-2-propanol (PP) is used as a preservative in cosmetics. PP is currently permitted to be used to up to 1% in cosmetic formulations in Korea and Europe. For risk assessment, percutaneous absorption is a crucial factor, but dermal absorption of PP has not yet been reported. In this study, Franz diffusion method was used to determine the percutaneous penetration of PP using the dorsal skin of rats. Each formulation of shampoo or cream, 113.6 mg/cm2, was applied to a donor compartment of Franz diffusion cell for 24 h. Receptor fluid was collected at 0, 1, 2, 4, 8, 12, and 24 h following dermal application. Remaining formulation was removed with a cotton swab after last sampling. Using tape stripping method, stratum corneum was removed. PP in epidermis and dermis was extracted in PBS for 24 h. The concentration of PP from the swab, stratum corneum, and epidermis and dermis samples was determined using high performance liquid chromatography. Total percutaneous absorption rates of PP for shampoo and cream were 50.0 ±â€¯6.0% and 33.0 ±â€¯3.2%, respectively. In vitro skin permeability was calculated as 1,377.2 ±â€¯240.1 mg/cm2 for shampoo and 1,038.0 ±â€¯72.2 mg/cm2 for cream for 24 h.

Pharmacokinetic Analysis of Intraocular Penetration of Latanoprost Solutions with Different Preservatives in Human Eyes.

PURPOSE: To investigate the effect of excipients on latanoprost penetration into the aqueous humor with clinically available 6 products with different solutions mainly in the types and concentrations of preservatives. METHODS: In 363 patients with cataracts, we instilled 1 latanoprost drop in 1 eye before surgery. The drop was randomly selected by brand name product (A) and 5 generic products (B-F) composed with different excipients. B contains similar excipients to A. C and D contain lower concentrations of benzalkonium chloride than A. E includes sodium benzoate, and F contains no preservatives. At 0.5-1, 3, and 6 h after instillation, samples of aqueous humor were collected to determine the latanoprost free acid by mass spectrometry. The time course of intraocular concentration and the areas under the aqueous humor latanoprost free acid concentration-time curves (AUCs) were calculated. RESULTS: At 0.5-1 h, the aqueous humor concentration of latanoprost free acid was 8.5 ± 1.0 ng/mL for C, which was significantly higher (P < 0.01) than that of A (3.4 ± 0.5 ng/mL). At 3 and 6 h, however, no significant difference was noted in the concentrations of latanoprost free acid between the brand name and generic products. For each of the generic products, the peak free acid concentration was above the known threshold concentration for biological activity. At 6 h postdose, however, the levels of latanoprost free acid were below the threshold for Products C, E, and F. Comparisons of AUC0-6h and AUC0-24h values showed that these parameters were the greatest with A, and E was significantly inferior to A (P < 0.05). CONCLUSIONS: Currently available latanoprost solutions with different preservatives showed sufficient intraocular concentration to activate the FP receptor, but different pharmacokinetic profiles of absorption or elimination.

Pharmacokinetics and Safety of Travoprost 0.004% Ophthalmic Solution Preserved with Polyquad in Pediatric Patients with Glaucoma.

PURPOSE: To evaluate the systemic pharmacokinetics (PKs) of travoprost 0.004% preserved with Polyquad® (TRAVATAN®) in pediatric patients with glaucoma or ocular hypertension. METHODS: This was a phase 1, open-label, multicenter clinical study of patients aged ≥2 months to <18 years. Patients received daily administration of travoprost 0.004% preserved with Polyquad in both eyes for 7 days. Plasma samples were collected 30 min before the final dose and at 10, 20, 40, and 80 min postdose. The main outcome measure was maximum concentration of travoprost free acid in plasma (Cmax). RESULTS: Included in the PK analysis were 24 patients (average age 9.6 ± 4.9 years). At least 1 sample with quantifiable levels of travoprost free acid was collected for 11 patients. The mean Cmax was 0.0471 ± 0.0105 ng/mL for patients aged 2 months to <3 years; 0.0258 ± 0.0128 ng/mL for ages 3 to <12 years; and 0.0109 ± 0.0005 ng/mL for ages 12 to <18 years. Travoprost was undetectable in samples collected predose from pediatric patients. Treatment-related adverse events (AEs) included hyperemia, eye pain, and eye pruritus (n = 1 each). There were no discontinuations or drug-related serious AEs. CONCLUSIONS: Travoprost free acid concentration in plasma was low in pediatric patients, detectable in only 11 of 24 patients. There was no accumulation of travoprost over the course of treatment. No clear relationship was observed between age/body surface area and Cmax. No increased risk was identified for the use of travoprost 0.004% preserved with Polyquad in patients <18 years of age.

Preparation and in vitro/in vivo evaluation of antimicrobial ocular in situ gels containing a disappearing preservative for topical treatment of bacterial conjunctivitis.

The study aimed to formulate and evaluate levofloxacin hemihydrate ocular in situ gels along with freshly prepared disappearing preservative reported to be safer to human eyes. Formulae were prepared using thermosensitive (PF127 and PF68) or ion-activated (Gelrite) polymers. They were evaluated for gelation temperature (GT), capacity, content uniformity, pH, rheological behavior, in vitro drug release with kinetic analysis. Best formulae were exposed to storage effect to select the optimum formula that was subjected to different sterilization methods and in vivo evaluation. The prepared disappearing preservative (sodium perborate monohydrate) proved to be active oxidative preservative and compatible with our formulae. F9 (24% PF127, 15% PF 68, 0.5% levofloxacin hemihydrate, and 0.0025% sodium perborate monohydrate) showed prolonged drug release (12 h), acceptable GT, viscosity, and pH. It remained stable over 3 months at two temperatures and was best sterilized by filtration. It showed longer residence time (12 h) in rabbits' eye fluids compared with the Levoxin® eye drops (4 h). This successful attempt of using thermo-gelling system along with a disappearing type of preservatives would allow the use of these systems to achieve sustained release of antimicrobial drugs with minimum risk of eye damage improving patient compliance and treatment efficacy.

Less Invasive Corneal Transepithelial Electrical Resistance Measurement Method.

PURPOSE: To evaluate acute corneal permeability changes after instillation of benzalkonium chloride (BAC) using a newly developed in vivo less invasive corneal transepithelial electrical resistance (TER) measurement method in animals and humans. METHODS: We previously developed an in vivo method for measuring corneal TER using intraocular electrodes in animals. This method can be used to precisely measure the decline of the corneal barrier function after instillation of BAC. To lessen the invasiveness of that procedure, we further refined the method for measuring the corneal TER by developing electrodes that could be placed on the surface of the cornea and in the conjunctival sac instead of inserting them into the anterior chamber. Corneal TER changes before and after exposure to 0.02% BAC were determined in this study using the new device in both rabbits and humans. RESULTS: There was a significant decrease in the corneal TER after exposure of the cornea to 0.02% BAC solution in both rabbits and humans (P<.01). The results of this new less invasive method agreed with those of formerly established anterior chamber methods in rabbit experiments. CONCLUSION: This new less invasive corneal TER measurement method enables us for the first time to measure TER of the human cornea, allowing safe and reliable investigation of the direct effect of different eye drop treatments on the corneal epithelium.

Transplacental passage of antimicrobial paraben preservatives.

Parabens are widely used preservatives suspected of being endocrine disruptors, with implications for human growth and development. The most common paraben found in consumer products is methylparaben. To date, no study has examined whether these substances cross the human placenta. A total of 100 study subjects (50 mother-child pairs) were enrolled at two medical institutions, serving primarily African-American and Caucasian women, respectively. A maternal blood sample was drawn on admission and a paired cord blood sample was obtained at delivery. Of the 50 mothers, 47 (94%) showed methylparaben in their blood (mean level 20.41 ng/l), and 47 in cords bloods (mean level 36.54 ng/l). There were 45 mother-child pairs where methylparaben was found in both samples. Of these, the fetal level was higher than the maternal level in 23 (51%). For butylparaben, only 4 mothers (8%) showed detectable levels (mean 40.54 ng/l), whereas 8 cord blood samples (16%) were positive (mean 32.5 ng/l). African-American mothers and infants showed higher prevalence of detectable levels (P=0.017). Methylparaben and butylparaben demonstrate transplacental passage. Additional studies are needed to examine potential differences in exposure by geography and demographics, what products are used by pregnant women that contain these preservatives, as well as any potential long-term effects in the growth and development of exposed children.

Benzalkonium chloride and glaucoma.

Glaucoma patients routinely take multiple medications, with multiple daily doses, for years or even decades. Benzalkonium chloride (BAK) is the most common preservative in glaucoma medications. BAK has been detected in the trabecular meshwork (TM), corneal endothelium, lens, and retina after topical drop installation and may accumulate in those tissues. There is evidence that BAK causes corneal and conjunctival toxicity, including cell loss, disruption of tight junctions, apoptosis and preapoptosis, cytoskeleton changes, and immunoinflammatory reactions. These same effects have been reported in cultured human TM cells exposed to concentrations of BAK found in common glaucoma drugs and in the TM of primary open-angle glaucoma donor eyes. It is possible that a relationship exists between chronic exposure to BAK and glaucoma. The hypothesis that BAK causes/worsens glaucoma is being tested experimentally in an animal model that closely reflects human physiology.

Dermal absorption and hydrolysis of methylparaben in different vehicles through intact and damaged skin: using a pig-ear model in vitro.

Currently, there is a trend to reduce of parabens use due to concern about the safety of their unmetabolised forms. This paper focused on dermal absorption rate and effectiveness of first-pass biotransformation of methylparaben (MP) under in-use conditions of skincare products. 24-h exposure of previously frozen intact and tapestripped (20 strips) pig-ear skin to nine vehicles containing 0.1% MP (AD, applied dose of 10 µg/cm²), resulted in 2.0-5.8%AD and 2.9-7.6%AD of unmetabolised MP, and 37.0-73.0%AD and 56.0-95.0%AD of p-hydroxybenzoic acid, respectively, in the receptor fluid. The absorption rate of MP was higher from emulsions than from hydrogels, from enhancer-containing vehicles than from enhancer-free vehicles, and when skin was damaged. Experiments confirmed that the freezing of pig-ear skin slightly reduces hydrolysis of MP. After 4-h exposure of intact freshly excised and intact frozen stored skin, amount of

Cytotoxicity of rigid gas-permeable lens care solutions.

PURPOSE: Reports on cytotoxic effects of rigid gas-permeable lens multipurpose solutions, which remain important because of increasing popularity of orthokeratology, are limited. This study determined cytotoxic effects of rigid gas-permeable lens multipurpose solutions on human corneal epithelial cells and assessed the proliferation rate at different levels of cell membrane damage. METHODS: The human corneal epithelial cells were exposed to multipurpose solutions containing chlorhexidine gluconate (0.003%) and polyaminopropyl biguanide (PHMB) (0.0005%) (MPS-A), PHMB (0.0005%) (MPS-B) and PHMB (0.0001%) (MPS-C) for one, five and 10 minutes. Following staining with Annexin V-FITC/7-AAD, cell viability and membrane integrity were assessed by flow cytometry. Effects of exposure to concentrations of 10 to 40 per cent multipurpose solutions for 12 hours on the metabolic rate of human corneal epithelial cells were assessed by 3-(4-,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. Recovery rates were assessed after re-culture for 96 hours at 37°C. RESULTS: MPS-A exposure caused the highest percentage of early and late necrotic cells for all exposure times and was significantly higher than other multipurpose solutions (p < 0.0001). After 10 minutes exposure, almost 40 per cent of cells in MPS-A but less than five per cent in MPS-B or MPS-C, were in late necrotic stage. After 12 hours of exposure, cell activity was significantly reduced in a dose-response manner for MPS-A treated cells only (p > 0.05). After 96 hours of re-culture, all exposed cells showed some reduction in viability but the effects of exposure to 30 and 40 per cent MPS-A resulted in loss of viability. CONCLUSION: The presence of chlorhexidine appeared to increase cytotoxicity of multipurpose solutions for rigid gas-permeable lenses. This was apparent in both increased levels of necrotic cells on initial exposure and reductions in viability after prolonged exposures at lower dilutions. Multipurpose solutions containing PHMB as a preservative, while not causing acute cytotoxicity, did affect cell viability following exposure to diluted solutions. This indicated it is inadvisable to expose the cornea to multipurpose solutions but rather to rinse lenses with saline before insertion and use artificial tears for rewetting.

Toxicity of ethylmercury (and Thimerosal): a comparison with methylmercury.

Ethylmercury (etHg) is derived from the metabolism of thimerosal (o-carboxyphenyl-thio-ethyl-sodium salt), which is the most widely used form of organic mercury. Because of its application as a vaccine preservative, almost every human and animal (domestic and farmed) that has been immunized with thimerosal-containing vaccines has been exposed to etHg. Although methylmercury (meHg) is considered a hazardous substance that is to be avoided even at small levels when consumed in foods such as seafood and rice (in Asia), the World Health Organization considers small doses of thimerosal safe regardless of multiple/repetitive exposures to vaccines that are predominantly taken during pregnancy or infancy. We have reviewed in vitro and in vivo studies that compare the toxicological parameters among etHg and other forms of mercury (predominantly meHg) to assess their relative toxicities and potential to cause cumulative insults. In vitro studies comparing etHg with meHg demonstrate equivalent measured outcomes for cardiovascular, neural and immune cells. However, under in vivo conditions, evidence indicates a distinct toxicokinetic profile between meHg and etHg, favoring a shorter blood half-life, attendant compartment distribution and the elimination of etHg compared with meHg. EtHg's toxicity profile is different from that of meHg, leading to different exposure and toxicity risks. Therefore, in real-life scenarios, a simultaneous exposure to both etHg and meHg might result in enhanced neurotoxic effects in developing mammals. However, our knowledge on this subject is still incomplete, and studies are required to address the predictability of the additive or synergic toxicological effects of etHg and meHg (or other neurotoxicants).

Uptake and release phenomena in contact lens care by silicone hydrogel lenses.

Contact lens solutions are highly complex mixtures of biocides (preservatives), surfactants, and other agents designed to disinfect, clean, and wet contact lenses. The commercialization of silicone hydrogel (SiHy) lenses has resulted in unique challenges to the manufacturers of contact lens solutions, because the properties of these materials differ markedly from those seen previously with poly-hydroxyethyl methacrylate-based hydrogels. Historically, hydrogel lens uptake and release of low-molecular weight preservatives such as chlorhexidine and thimerosal were known to result in allergic reactions, resulting in corneal irritation, stinging, conjunctival hyperemia, development of corneal infiltrates, palpebral lid changes, and corneal staining. However, little is known about the interaction of modern care systems with modern soft lens materials. Factors to be considered when evaluating the uptake and release of care components include the water content, charge, relative hydrophobicity, surface treatment, and porosity of the lens material, in conjunction with the concentration, charge/molecule, ionicity in the product matrix, molecular weight, and hydrophobicity of the care component in question. These factors control the sorption of the solution components by lenses, resulting in a variety of differences in the amount of the component taken up into the lens material and the amount and rate of subsequent release onto the ocular surface. Because both natural (ocular) and environmental biota become part of the solution-lens system during regimen use of any lens care product, these extraneously introduced substances should also be considered regarding their potential for uptake and either subsequent release onto the ocular surface or functioning as a scaffold for the adhesion of microbes. This article will review current knowledge concerning these interactions and investigate what clinically observable complications may arise from these interactions. It also reviews whether current methods to determine these interactions could be improved on.