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Consumer product manufacturers utilise a spectrum of alternative ocular irritation assays, as these tests do not require the use of live animals. Despite their usefulness, no regulatory-accepted assay assesses the reversibility of ocular damage, a key criterion of GHS ocular classification, like the rabbit eye test (i.e., Draize Rabbit Eye Test [DRET]). The Porcine Corneal Opacity Reversibility Assay (PorCORA), an ex vivo intact corneal tissue culture model, predicts the reversibility of damage by ocular irritants. Inclusion of the damage reversibility endpoint in the PorCORA supplements other alternative test methods for ocular irritation, by assessing induced eye damage and the ability of this damage to reverse (heal) without the use of live animals to distinguish between Globally Harmonised System of Classification and Labelling of Chemicals (GHS) ocular classifications. In this focused study, results of a Bovine Corneal Opacity and Permeability (BCOP) test of a laundry detergent, neat and 10% dilution, (product mixture from S.C. Johnson & Son, Inc. [SCJ]) classified the product into GHS Category 1; however, the BCOP test cannot assess the reversibility of ocular damage. The laundry detergent was evaluated using the PorCORA, where ocular damage induced by the detergent was fully reversed within seven days. Evaluation of the reversibility of ocular damage using the PorCORA in this focused study can add strength to the weight-of-evidence (WoE) analysis approach in ocular hazard assessment. This WoE approach strengthens the argument that the PorCORA can be used to supplement BCOP data, and that this laundry detergent is not an irreversible eye irritant. [ABSTRACT FROM AUTHOR]

Recently, we showed that the addition of physiological concentrations of ascorbic acid, a tear antioxidant, to the OptiSafe™ macromolecular eye irritation test reduced the false-positive (FP) rate for chemicals that had reactive chemistries, leading to the formation of reactive oxygen species (ROS) and molecular crosslinking. The purpose of the current study was to 1) increase the number of chemicals tested to comprehensibly determine whether the antioxidant-associated reduction in OD is specific to FP chemicals associated with ROS chemistries and 2) determine whether the addition of antioxidants interferes with the detection of true positive (TP) and true negative (TN) ocular irritants. We report that when ascorbic acid is added to the test reagents, retesting of FP chemicals with reactive chemistries show significantly reduced OD values (P

The purpose of this study was to develop Globally Harmonized System (GHS) and U.S. Environmental Protection Agency (EPA) prediction models for classifying irritant materials based on histopathologic in vitro depth of injury (DoI) measurements. Sixteen different materials were selected, representing all classes of toxicity, according to the GHS and EPA classification systems. Food-source rabbit eyes, similar to eyes used for the widely accepted Bovine Corneal Opacity and Permeability and Isolated Chicken Eye ocular irritation tests, were used. Tissues were exposed to test material for 1 min, and corneas were collected at 3- and 24-hours post-exposure. Tissues were then fixed and processed for live/dead biomarker fluorescent staining using phalloidin. DoI was then measured, and the percent DoI values for the epithelium and stroma were compared to the EPA and GHS classifications. Excluding surfactants, EPA nonclassified (category IV) materials showed no stromal and very slight epithelial damage (≤10%) to the cornea, whereas EPA corrosive (category I) materials showed significantly greater damage (P 10%, P

OptiSafeTM (OS) is a shelf stable, nonanimal test for ocular irritation. A recent database search found that half of the OS false positive (FP) materials were associated with reactive oxygen chemistries but were not eye irritants in vivo (based on historical rabbit studies by other groups). We hypothesized that naturally occurring tear antioxidants protect the eye from reactive chemistries in vivo and that specific tear chemistries might help explain why some materials are FP for nonanimal tests but are reported as nonirritants in the live animal. To test this hypothesis, a prior study evaluated tear antioxidants and found that the tear antioxidant ascorbic acid, added at human physiological tear levels to the OS test, specifically reduced the measured values for these FPs but did not reduce the true-positive rate. Based on these findings, the OS test method was further optimized. The purpose of the current study was to comprehensively evaluate the performance of the further optimized test method for detection of ocular irritants. The OS test measures chemically induced damage to macromolecules and relates these measured values to ocular irritancy. To improve the performance of OS, we made updates to the material to be tested physiochemical handling procedures, prediction model, and test method to include tear-level concentrations of ascorbic acid. We then retested the 78 chemicals from the prior OS-coded validation study in triplicate and compared the accuracy of the 'nonirritant versus irritant' prediction for the further optimized method with the prior results. We report that for the detection of 'nonirritant' versus 'irritant' (GHS NC versus categories 2B/A and 1) test substances, the further optimized OS test with ascorbic acid compared with the original version has a FP rate that is reduced from 40.0 to 22.2%, the false-negative (FN) rate remains at 0.0%, and the accuracy improved from 80.3% to 89.2%. A comparison to OECD-adopted tests demonstrates that the further optimized OS test, like the original method, has a higher accuracy and lower FN rate for the detection of 'nonirritants' versus 'irritants' (GHS Category NC versus 2B/A and 1) than the other eye irritation tests (BCOP, EpiOcularTM Eye Irritation Test, ICE, Ocular Irritection®, and STE). [ABSTRACT FROM AUTHOR]

Background: Ocular irritation remains the main disadvantage of the sutured conjunctival graft after pterygium excision. Evaluation of the severity of these manifestations can be helpful for better patient counselling about the expected postoperative course. Aim: To evaluate the manifestations of ocular irritation in patients treated by pterygium excision with sutured conjunctival autograft. Setting: A prospective interventional case series that evaluated the postoperative manifestations of ocular irritation in pterygium patients. Methods: Twenty-five pterygium patients were treated by pterygium excision with vicryl 8/0 sutured conjunctival autograft. The severity of postoperative foreign body sensation, pain, watering, and localised hyperemia involving the nasal conjunctival quadrant were evaluated, scored, and graded. Results: The main reported symptom was foreign body sensation, with a mean grade of 1.9 ± 0.54 recorded 3 to 4 days postoperatively, which declined one week postoperatively to a mean of 1 ± 0.45. Mild to moderate tolerable symptoms were reported in 92% at the first postoperative visit with an average score of 5 ± 1.05, which declined to an average of 1.4 ± 0.52 at one week, with all the patients reporting minimal symptoms. At the end of the follow-up, the mean index of localised nasal conjunctival hyperaemia was 2.5 ± 0.39. Recurrence was recorded in one patient (4%). No other complications were encountered. Conclusion: Sutured conjunctival autograft can be used safely with tolerable short-term minimal to moderate manifestations of ocular irritation with no significant complications.

As drug delivery to the eye has evolved over the last decades, researchers have explored more effective treatments for ocular diseases. Despite this, delivering drugs to the cornea remains one of the most problematic issues in ophthalmology due to the poor permeability of the cornea and tear clearance mechanisms. In this study, four different types of polyaphron formulations are prepared with 10% poloxamer 188 (P188), 10% poly(2-ethyl-2-oxazoline), 1% polyquaternium 10, and 3% sodium carboxymethylcellulose solutions mixed with 1% Brij® L4 in a caprylic/capric triglycerides solution. Their physicochemical characteristics, rheological properties, and stability are assessed. Additionally, a polyaphron with 3% polyquaternium 10 was prepared for the assessment of ex vivo corneal retention along with four other polyaphrons. The best retention on the ex vivo cornea was displayed by the 3% polyquaternium 10-based formulation. The 10% poloxamer 188 along with 1% polyquaternium 10-based polyaphrons appeared to be the most stable among the four prepared formulations. A toxicological evaluation of these formulations was performed using a slug mucosal irritation test and bovine corneal opacity and permeability assay, with all four polyaphrons proving good biocompatibility with ocular tissues. The developed drug delivery systems demonstrated an excellent potential for ocular drug delivery. [ABSTRACT FROM AUTHOR]

Aim: The objective of the presented study is to evaluate the acute dermal and ocular irritation of herbal shampoos consisting of a mixture of plant extracts. Materials and Methods: Both studies performed using New Zealand white rabbits in accordance with HICS and OECD guidelines respectively. In the cutaneous skin irritation test, erythema, eschar or edema evaluated. In the ocular irritation study, corneal opacity, area of opacity, iris, chemosis and conjunctival redness were evaluated. Results: In the cutaneous skin irritation test, all three herbal shampoos (PS9, PS20, and LS17) showed no significant erythema, eschar, or oedema formation after 72 hr of exposure and did not meet any of the irritation classification requirements. According to the Harmonized Integrated Classification System (HICS), all three herbal shampoos are classified as "Non Irritant" based on acute cutaneous testing. In the ocular irritation study, after 1, 24, 48, and 72 hr of observation, the treated eye appeared normal. There were no symptoms of systemic toxicity in any of the animals during the acclimatization and post-treatment periods. The results did not meet the irritation classification requirements for categories 1, 2A, or 2B because the treated animals had corneal opacity of 0.00, iris lesions of 0.00, conjunctival redness of 0.00, and chemosis of 0.00. Based on ocular irritation studies, all three herbal shampoos are classified as "Not Irritant" by HICS. The body weights of all the animals were within the typical range of variation for this species, strain, and age. All of the animals gained weight towards the end of the experiments. Conclusion: The acute cutaneous and ocular irritation studies indicated that three herbal shampoos (PS9, PS20, and LS17) were not irritant to the rabbit skin or eyes, indicating that they can be used in humans without irritation to the skin or eye. [ABSTRACT FROM AUTHOR]

Background: Ocular irritation remains the main disadvantage of the sutured conjunctival graft after pterygium excision. Evaluation of the severity of these manifestations can be helpful for better patient counselling about the expected postoperative course. Aim: To evaluate the manifestations of ocular irritation in patients treated by pterygium excision with sutured conjunctival autograft. Setting: A prospective interventional case series that evaluated the postoperative manifestations of ocular irritation in pterygium patients. Methods: Twenty-five pterygium patients were treated by pterygium excision with vicryl 8/0 sutured conjunctival autograft. The severity of postoperative foreign body sensation, pain, watering, and localised hyperemia involving the nasal conjunctival quadrant were evaluated, scored, and graded. Results: The main reported symptom was foreign body sensation, with a mean grade of 1.9 ± 0.54 recorded 3 to 4 days postoperatively, which declined one week postoperatively to a mean of 1 ± 0.45. Mild to moderate tolerable symptoms were reported in 92% at the first postoperative visit with an average score of 5 ± 1.05, which declined to an average of 1.4 ± 0.52 at one week, with all the patients reporting minimal symptoms. At the end of the follow-up, the mean index of localised nasal conjunctival hyperaemia was 2.5 ± 0.39. Recurrence was recorded in one patient (4%). No other complications were encountered. Conclusion: Sutured conjunctival autograft can be used safely with tolerable short-term minimal to moderate manifestations of ocular irritation with no significant complications. [ABSTRACT FROM AUTHOR]

As drug delivery to the eye has evolved over the last decades, researchers have explored more effective treatments for ocular diseases. Despite this, delivering drugs to the cornea remains one of the most problematic issues in ophthalmology due to the poor permeability of the cornea and tear clearance mechanisms. In this study, four different types of polyaphron formulations are prepared with 10% poloxamer 188 (P188), 10% poly(2-ethyl-2-oxazoline), 1% polyquaternium 10, and 3% sodium carboxymethylcellulose solutions mixed with 1% Brij® L4 in a caprylic/capric triglycerides solution. Their physicochemical characteristics, rheological properties, and stability are assessed. Additionally, a polyaphron with 3% polyquaternium 10 was prepared for the assessment of ex vivo corneal retention along with four other polyaphrons. The best retention on the ex vivo cornea was displayed by the 3% polyquaternium 10-based formulation. The 10% poloxamer 188 along with 1% polyquaternium 10-based polyaphrons appeared to be the most stable among the four prepared formulations. A toxicological evaluation of these formulations was performed using a slug mucosal irritation test and bovine corneal opacity and permeability assay, with all four polyaphrons proving good biocompatibility with ocular tissues. The developed drug delivery systems demonstrated an excellent potential for ocular drug delivery.

OptiSafe is an in chemico test method that identifies potential eye irritants based on macromolecular damage following test chemical exposure. The OptiSafe protocol includes a prescreen assessment that identifies test chemicals that are outside the applicability domain of the test method and thus determines the optimal procedure. We assessed the usefulness and limitations of the OptiSafe test method for identifying chemicals not requiring classification for ocular irritation (i.e. bottom-up testing strategy). Seventeen chemicals were selected by the lead laboratory and tested as an independent study. Ninety-five unique coded chemicals were selected by a validation management team to assess the intra- and interlaboratory reproducibility and accuracy of OptiSafe in a multilaboratory, three-phased validation study. Three laboratories (lead laboratory and two naïve laboratories) evaluated 35 chemicals, with the remaining 60 chemicals evaluated by the lead laboratory only. Test method performance was assessed by comparing classifications based on OptiSafe results to classifications based on available retrospective in vivo data, using both the EPA and GHS eye irritation hazard classification systems. No prospective in vivo testing was conducted. Phase I testing of five chemicals showed that the method could be transferred to naïve laboratories; within-lab reproducibility ranged from 93% to 100% for both classification systems. Thirty coded chemicals were evaluated in Phase II of the validation study to demonstrate both intra- and interlaboratory reproducibility. Intralaboratory reproducibility for both EPA and GHS classification systems for Phase II of the validation study ranged from 93% to 99%, while interlaboratory reproducibility was 91% for both systems. Test method accuracy for the EPA and GHS classification systems based on results from individual laboratories ranged from 82% to 88% and from 78% to 88%, respectively, among the three laboratories; false negative rates ranged from 0% to 7% (EPA) and 0% to 15% (GHS). When results across all three laboratories were combined based on the majority classification, test method accuracy and false negative rates were 89% and 0%, respectively, for both classification systems, while false positive rates were 25% and 23% for the EPA and GHS classification systems, respectively. Validation study Phase III evaluation of an additional 60 chemicals by the lead laboratory provided a comprehensive assessment of test method accuracy and defined the applicability domain of the method. Based on chemicals tested in Phases II and III by the lead laboratory, test method accuracy was 83% and 79% for the EPA and GHS classification systems, respectively; false negative rates were 4% (EPA) and 0% (GHS); and false positive rates were 40% (EPA) and 42% (GHS). Potential causes of false positives in certain chemical (e.g. ethers and alcohols) or hazard classes are being further investigated. The OptiSafe test method is useful for identifying nonsurfactant substances not requiring classification for ocular irritancy. OptiSafe represents a new tool for the in vitro assessment of ocular toxicity in a tiered-testing strategy where chemicals can be initially tested and identified as not requiring hazard classification. [ABSTRACT FROM AUTHOR]

The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In the present study, we developed and evaluated a thermosensitive gelling system based on a selenium-containing polymer for topical ocular continuous drug release. In detail, di-(1-hydroxylundecyl) selenide (DHSe), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) were polymerized to form poly(DHSe/PEG/PPG urethane). The polymer was used to carry poorly water-soluble remdesivir (RDV) at room temperature to form the final thermosensitive in situ gel, which exhibited a typical sol-gel transition at 35 °C. The formed polymer was further characterized by rheology, thermology, and scanning electron microscopy. In vitro release studies and in vivo retention and penetration tests indicated that the thermogel provided the prolonged release of RDV. The RDV-loaded in situ gel was proven to be non-biotoxic against human corneal epithelial cells, with good ocular tolerance and biocompatibility in rabbit eyes.

The “Peira LLBO 180” is a Laser Light-Based Opacitometer that can be used as an alternative for the standard OP-KIT device in the Bovine Corneal Opacity and Permeability (BCOP) test Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) 437 to identify chemicals inducing serious eye damage as defined by United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS), i.e. chemicals to be classified as UN GHS Category 1 and chemicals not requiring classification for eye irritation or serious eye damage under the UN GHS classification system (No Category).• The Peira LLBO 180 offers the advantage of analysing the complete corneal surface and is therefore able to detect more efficiently opaque spots located around the periphery of the excised corneas.• This new device will allow not only a more accurate definition of the eye irritating potential of compounds, but also a more precise ranking of moderate to mild and non-irritating compounds.• The value of Peira LLBO 180 is confirmed during in-house and multi-laboratory evaluation studies and is now included in the updated OECD TG 437, dated 26th of June 2020.The results demonstrate that the presented methodology is an improved new approach methodology (NAM) for ocular irritation testing of liquids and solids.

Abstract Keratinocyte growth factor −2 promotes corneal repair. Its mechanism of action involves regulating regeneration and migration of corneal cells, as well as activating corneal limbal stem cells. However, KGF-2 being a carcinogenic growth factor and its potential adverse effect in over dosage long-term treatment had not yet been reported. In this study, we used New Zealand white rabbits to study possible toxic effects of ocular administration of recombinant human keratinocyte growth factor-2 eye drops. Animals in the medium- and high-dose groups had some ocular irritant reactions during the course of drug administration; however this reaction was harmless to the cornea and it ended up when administration was stopped. Serum biochemistries were largely unaffected by treatment. Pathological examinations were unremarkable. We found that over-dosed administration of these eye drops caused some ocular irritation, but this irritant reaction was harmless to the eye, and it reversed after the drug was stopped. There were no apparent systemic effects of the drug. Graphical abstract Image 1 Highlights • It was the first time to do the long-term toxicology study of rhKGF-2 eye drops. • Eye irritation was the main adverse reactions of high dose of rhKGF-2 eye drops. • Long-term using of rhKGF-2 eye drops has no excessive corneal proliferation risk. • Long-term adminstration of rhKGF-2 eye drops was safety. [ABSTRACT FROM AUTHOR]

Aim: This investigation aimed to develop a voriconazole-loaded chitosan-coated cationic microemulsion (CVME) to treat fungal keratitis. Methods: Microemulsions were prepared using water titration, and the optimized microemulsion was coated with chitosan to prepare CVME. The physicochemical parameters, ocular irritation potential, in vitro antifungal efficacy and in vitro release studies were performed. The in vivo antifungal efficacy study was conducted in a fungal infection-induced rabbit eye model. Results: The developed CVME displayed acceptable physicochemical properties and excellent mucoadhesive behavior and showed a sustained release profile. Ex vivo and in vivo studies concluded that higher permeability and improved antifungal efficacy were observed for CVME than drug suspension (DS). Conclusion: The prepared CVME7 is a viable alternative to treating fungal keratitis with existing approaches.

Assessment of ocular irritation potential is an international regulatory requirement in the safety evaluation of industrial and consumer products. None in vitro ocular irritation assays are capable of fully categorizing chemicals as stand-alone. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI consortium assessed the reliability of eight in vitro test methods and computational models as well as established a tiered-testing strategy. One of the selected assays was Bovine Corneal Opacity and Permeability (BCOP). In this project, the same corneas were used for measurement of opacity using the OP-KIT, the Laser Light-Based Opacitometer (LLBO) and for histopathological analysis. The results show that the accuracy of the BCOP OP-KIT in identifying Cat 1 chemicals was 73.8% while the accuracy was 86.3% for No Cat chemicals. BCOP OP-KIT false negative results were often related to an in vivo classification driven by conjunctival effects only. For the BCOP LLBO, the accuracy in identifying Cat 1 chemicals was 74.4% versus 88.8% for No Cat chemicals. The BCOP LLBO seems very promising for the identification of No Cat liquids but less so for the identification of solids. Histopathology as an additional endpoint to the BCOP test method does not reduce the false negative rate substantially for in vivo Cat 1 chemicals. [ABSTRACT FROM AUTHOR]

Assessment of acute eye irritation potential is part of the international regulatory requirements for safety testing of chemicals. In the last decades, many efforts have been made in the search for alternative methods to replace the regulatory in vivo Draize rabbit eye test (OECD TG 405). Success in terms of complete replacement of the regulatory in vivo Draize rabbit eye test has not yet been achieved. The main objective of the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was to develop tiered testing strategies for serious eye damage and eye irritation assessment that can lead to complete replacement of OECD TG 405. A set of 80 reference chemicals ( e . g . balanced by important driver of classification and physical state), was tested with seven test methods. Based on the results of this project, three different strategies were suggested. We have provided a standalone (EpiOcular ET-50), a two-tiered and three-tiered strategy, that can be used to distinguish between Cat 1 and Cat 2 chemicals and chemicals that do not require classification (No Cat). The two-tiered and three-tiered strategies use an RhCE test method (EpiOcular EIT or SkinEthic™ EIT) at the bottom (identification No Cat) in combination with the BCOP LLBO (two-tiered strategy) or BCOP OP-KIT and SMI (three-tiered strategy) at the top (identification Cat 1). For our proposed strategies, 71.1% - 82.9% Cat 1, 64.2% - 68.5% Cat 2 and ≥ 80% No Cat chemicals were correctly identified. Also, similar results were obtained for the Top-Down and Bottom-Up approach. [ABSTRACT FROM AUTHOR]

Assessment of the acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. In the past, several prospective and retrospective validation studies have taken place in the area of serious eye damage/eye irritation testing. Success in terms of complete replacement of the regulatory in vivo Draize rabbit eye test has not yet been achieved. A very important aspect to ensure development of successful alternative test methods and/or strategies for serious eye damage/eye irritation testing is the selection of appropriate reference chemicals. A set of 80 reference chemicals was selected for the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project, in collaboration with Cosmetics Europe, from the Draize Reference Database published by Cosmetics Europe based on key criteria that were set in their paper ( e.g. balanced by important driver of classification and physical state). The most important goals of the CON4EI project were to identify the performance of eight in vitro alternative tests in terms of driver of classification and to identify similarities/differences between the methods in order the build a successful testing strategy that can discriminate between all UN GHS categories. This paper provides background on selection of the test chemicals. [ABSTRACT FROM AUTHOR]

Assessment of ocular irritation is a regulatory requirement in safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as stand-alone assays. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed to assess the reliability of eight in vitro test methods and computational models as well as establishing an optimal tiered-testing strategy. For three computational models (Toxtree, and Case Ultra EYE_DRAIZE and EYE_IRR) performance parameters were calculated. Coverage ranged from 15 to 58%. Coverage was 2 to 3.4 times higher for liquids than for solids. The lowest number of false positives (5%) was reached with EYE_IRR; this model however also gave a high number of false negatives (46%). The lowest number of false negatives (25%) was seen with Toxtree; for liquids Toxtree predicted the lowest number of false negatives (11%), for solids EYE_DRAIZE did (17%). It can be concluded that the training sets should be enlarged with high quality data. The tested models are not yet sufficiently powerful for stand-alone evaluations, but that they can surely become of value in an integrated weight-of-evidence approach in hazard assessment. [ABSTRACT FROM AUTHOR]

Assessment of ocular irritancy is an international regulatory requirement in the safety evaluation of industrial and consumer products. Although many in vitro ocular irritation assays exist, alone they are incapable of fully categorizing chemicals. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI consortium was developed to assess the reliability of eight in vitro test methods and establish an optimal tiered-testing strategy. One assay selected was the Short Time Exposure (STE) assay. This assay measures the viability of SIRC rabbit corneal cells after 5 min exposure to 5% and 0.05% solutions of test material, and is capable of categorizing of Category 1 and No Category chemicals. The accuracy of the STE test method to identify Cat 1 chemicals was 61.3% with 23.7% sensitivity and 95.2% specificity. If non-soluble chemicals and unqualified results were excluded, the performance to identify Cat 1 chemicals remained similar (accuracy 62.2% with 22.7% sensitivity and 100% specificity). The accuracy of the STE test method to identify No Cat chemicals was 72.5% with 66.2% sensitivity and 100% specificity. Excluding highly volatile chemicals, non-surfactant solids and non-qualified results resulted in an important improvement of the performance of the STE test method (accuracy 96.2% with 81.8% sensitivity and 100% specificity). Furthermore, it seems that solids are more difficult to test in the STE, 71.4% of the solids resulted in unqualified results (solubility issues and/or high variation between independent runs) whereas for liquids 13.2% of the results were not qualified, supporting the restriction of the test method regarding the testing of solids. [ABSTRACT FROM AUTHOR]

Objective: Propylene glycol (PG) is a widely used solvent, chemical intermediate and carrier substance for foods, pharmaceutical and cosmetic products. Professional and occupational exposure to PG aerosol and vapor may occur from theatrical smoke generators and during application of deicing products to airplanes. While PG is considered to have low toxicity, the results of one study suggested that brief (1-min) exposure to PG mist elicited ocular and respiratory effects in humans. Because the high concentrations and brief exposure duration in that study were not representative of most occupational exposures, a controlled experimental exposure study was conducted to clarify or confirm the earlier findings. Materials and methods: Ten males and 10 females were exposed to PG aerosol for 4 hrs at 20 and 100 mg/m3 and 30 min at 200 mg/m3. Total PG exposure concentrations (droplets plus gas phase) were 95.6, 442.4 and 871 mg/m3 for the three conditions, respectively. Participants rode a stationary bicycle to simulate physical effort at regular intervals during exposure. Objective measures evaluated in this study included ocular irritation via eye blink task and eye photography and pulmonary function via spirometry, while subjective measures included health symptoms ratings, irritation and dryness ratings of eyes, nose, throat and mouth. Results: Objective measures of pulmonary function and ocular irritation did not reveal any exposure-related changes. Exposure-related changes in symptom reporting were observed; however, the highest symptom ratings did not exceed “slight” on the scale. Conclusions: The results indicate at the concentrations and acute durations tested, PG does not affect human respiratory function or produce ocular irritation. [ABSTRACT FROM AUTHOR]

Tacrolimus (TAC)-loaded Ploy-lactide-co-glycolide nanoparticles (PLGA-NPs) was developed by emulsification-diffusion method for topical ocular delivery in certain ocular conditions where therapeutic level of immunomodulator into eyes is required for sufficient duration. So, we optimized TAC-loaded PLGA-NPs with higher TAC payload. The mean particle-size and its distribution, polydispersity, zeta-potentials, morphology, drug encapsulation and loading capacity of NPs were analyzed. Transcorneal permeation through excised rabbit cornea revealed instant and controlled permeation of TAC from TAC-aqueous suspension (TAC-AqS) and from PLGA-NPs, respectively. Stability study results indicated that there were no significant changes in above characteristics for 1-month storage at 25 °C. The safety of PLAG was established by modified Draize’s test after its topical administration in rabbit eyes. The adopted liquid chromatography-electrospray ionization tandem mass spectrometry was successfully applied for TAC quantification in ocular tissues and aqueous-humor. PLGA-NPs improved corneal, conjunctival and aqueous humor bioavailability of TAC. A considerably higher TAC-concentration from F2 was found in ocular tissues even at 24 h and in aqueous humor till 24 h following its topical ocular administration as compared to TAC-AqS. The PLGA-NPs significantly enhanced ocular bioavailability of TAC than that of aqueous suspension. [ABSTRACT FROM AUTHOR]

Assessment of ocular irritation potential is an international regulatory requirement in the safety evaluation of industrial and consumer products. None in vitro ocular irritation assays are capable of fully categorizing chemicals as stand-alone. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI consortium assessed the reliability of eight in vitro test methods and computational models as well as established a tiered-testing strategy. One of the selected assays was Bovine Corneal Opacity and Permeability (BCOP). In this project, the same corneas were used for measurement of opacity using the OP-KIT, the Laser Light-Based Opacitometer (LLBO) and for histopathological analysis. The results show that the accuracy of the BCOP OP-KIT in identifying Cat 1 chemicals was 73.8% while the accuracy was 86.3% for No Cat chemicals. BCOP OP-KIT false negative results were often related to an in vivo classification driven by conjunctival effects only. For the BCOP LLBO, the accuracy in identifying Cat 1 chemicals was 74.4% versus 88.8% for No Cat chemicals. The BCOP LLBO seems very promising for the identification of No Cat liquids but less so for the identification of solids. Histopathology as an additional endpoint to the BCOP test method does not reduce the false negative rate substantially for in vivo Cat 1 chemicals. [ABSTRACT FROM AUTHOR]

Assessment of the acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. In the past, several prospective and retrospective validation studies have taken place in the area of serious eye damage/eye irritation testing. Success in terms of complete replacement of the regulatory in vivo Draize rabbit eye test has not yet been achieved. A very important aspect to ensure development of successful alternative test methods and/or strategies for serious eye damage/eye irritation testing is the selection of appropriate reference chemicals. A set of 80 reference chemicals was selected for the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project, in collaboration with Cosmetics Europe, from the Draize Reference Database published by Cosmetics Europe based on key criteria that were set in their paper ( e.g. balanced by important driver of classification and physical state). The most important goals of the CON4EI project were to identify the performance of eight in vitro alternative tests in terms of driver of classification and to identify similarities/differences between the methods in order the build a successful testing strategy that can discriminate between all UN GHS categories. This paper provides background on selection of the test chemicals. [ABSTRACT FROM AUTHOR]

Melatonin (MT), an effective antioxidant, has therapeutic implications for granular corneal dystrophy type 2 (GCD2) treatment. Eye drop formulations containing cyclodextrins (CDs) were studied with the objective of improving MT solubility, stability, and ocular absorption, while decreasing eye irritation. MT complexes with αCD, βCD, γCD, and 2-hydroxypropyl-βCD (HPβCD) were characterized by phase solubility studies, which demonstrated Higuchi’s A L -type phase solubility profiles. The MT/HPβCD complex showed the highest MT solubility (2.75 mg/mL). Ocular irritation experiments showed HPβCD inclusion alleviated irritation of the eye. After administration of MT formulations to rabbit corneas, each harvested cornea was separated into corneal epithelium, stroma, and endothelium. MT concentrations in the corneal epithelium, stroma, and endothelium for the F1-treated group were 55.5 ± 9.24, 26.7 ± 2.66, and 21.1 ± 1.77 μM while those for the F2-treated group were 127.2 ± 21.01, 43.7 ± 16.93, and 51.0 ± 13.91 μM, respectively. Stability studies for 60 days showed no significant change in pH, osmolarity, and MT content. In conclusion, MT/HPβCD formulations can lower irritation, enhance MT stability, and improve therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Conjunctivitis is one of the most common infection met in ophthalmology practice, with three major types: bacterial, viral and allergic. Patients with conjunctivitis commonly present with red eyes, ocular irritation, tearing, foreign body sensation, burning, itching and ocular discharge. Symptoms and signs may present unilaterally or bilaterally. If the patient complaints are pain, acute foreign body sensation and photophobia, we have corneal involvement. It is usually highly contagious and the treatment is empirical and supportive. [ABSTRACT FROM AUTHOR]

The aim of this work was to determine the correlation between results obtained from the Draize test and from the Total Protein Content Determination (TPC) to assess the ocular irritancy potential of 20 shampoos. For TPC, two established cell lines (SIRC and 3T3) were used. The concentration that induced 50% inhibition relative to controls (IC50) was calculated for each product. Among shampoos tested with SIRC, only one had a false positive result. However, for the 3T3, three false-negative results were found. Pearson coefficient related to the in vivo value of maximum average score (MAS) was -0.58 (p=0.007) with SIRC and -0.73 (p=0.007) with 3T3. These results showed that the TPC assay was capable to predict the ocular irritant potential of shampoos, and therefore was a promissory tool to be used as a preliminary assay for the detection of irritant products and to be part of a battery of screening tests to minimize the animal use in the Draize Test.

The OptiSafe (OS) test is shelf-stable, macromolecular eye irritation test that does not include any animal ingredient or component ("vegan"). The purpose of this study was to evaluate the test's accuracy for an expanded application domain for both the original and recently updated OS method. This study involved the testing of additional ocular corrosives and previously excluded foaming agents ("surfactants") using both the original and updated OS methods and then combining these data with prior validation data for a total of 147 chemicals. Predictivity was evaluated by a statistical comparison of the OptiSafe predictions with historical in vivo "Draize" rabbit eye data for the same chemicals (from public databases). We report that for the detection of chemicals not requiring classification for eye irritation [Globally Harmonized System of Classification and Labeling of Chemicals (GHS) No Category], the accuracy, specificity, and sensitivity were 92.8%, 79.6%, and 100.0%, respectively, for the updated method; for the detection of chemicals inducing extreme eye damage/corrosion (GHS Category 1), the accuracy, specificity, and sensitivity were 79.4%, 71.8%, and 91.7%, respectively, for the updated method. Results indicate that both the original and updated methods have a high accuracy for the expanded application domain that included ocular corrosives and surfactants. • The OptiSafe nonanimal eye irritation test application domain was expanded to include surfactants and ocular corrosives. • For the detection of chemicals not requiring classification for eye irritation (GHS No Category), the accuracy, specificity, and sensitivity were 92.8%, 79.6%, and 100.0%, for the updated OptiSafe method. • For the detection of chemicals inducing extreme eye damage/corrosion (GHS Category 1), the accuracy, specificity, and sensitivity were 79.4%, 71.8%, and 91.7%, for the updated OptiSafe method. [ABSTRACT FROM AUTHOR]