The eye irritation test and pharmacokinetic study of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits / 药学实践杂志

Objective To study the eye irritation and the pharmacokinetics of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits. Methods The eye irritation of tacrolimus-loaded cationic nanoemulsion-based in-situ gel in rabbits was observed by histological cross-sections of external ocular tissues stained with HE. The aqueous humor of rabbit eyes was extracted by corneal puncture and analyzed by HPLC-MS for pharmacokinetic study. Results Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had no significant irritation on rabbit eyes. The pharmacokinetic parameter showed that the AUC of tacrolimus-loaded cationic nanoemulsion-based in-situ gel was (128.34±13.09) ng·h/ml, which was 1.13 times of tacrolimus-loaded cationic nanoemulsion (113.61±12.36) ng·h/ml and 1.88 times of Talymus® (68.25±10.82) ng·h /ml. Conclusion Tacrolimus-loaded cationic nanoemulsion-based in-situ gel had the advantages of low irritation, long retention time and high bioavailability in rabbit eyes. It has a good potential for clinical application.

Application of bovine corneal opacity and permeability test in the eye irritation evaluation of cosmetics / 上海预防医学

Objective To establish bovine corneal opacity and permeability （BCOP） test， and determine its predictive ability for the eye irritation evaluation of cosmetics. Methods A total of ten reference chemicals were selected to establish the BCOP test. Then eye irritation of 16 routinely collected cosmetics in our laboratory was predicted. In vitro scores were calculated by the change in the opacity and sodium fluorescein permeability after exposure to the testing cosmetics， and subsequently compared with the historical data by Draize test. Results Reference chemicals with known irritation classification were correctly classified by the BCOP test， which was consistent with the classification of UN globally harmonized system of classification and labeling of chemicals. Moreover， the specificity of the BCOP test for the classification of non-irritating cosmetics samples was 80.0% （8/10）， and the sensitivity for weak to mild irritating cosmetics samples was 83.3% （5/6）. The BCOP test demonstrated an overall classification consistency of 81.3% （13/16） with in vivo test. Conclusion BCOP test may be independently used to identify chemicals with potential eye irritation and serious eye damage， suggesting it is significant for in vitro integrated test strategy for predicting eye irritation due to cosmetics.

Scientific Analysis of Processing of Pinelliae Rhizoma by Ancient Hot Water Washing Method / 中国实验方剂学杂志

Objective:To evaluate the scientificity and feasibility of processing of Pinelliae Rhizoma by hot water washing （Tangxi）， and to provide reference for the development of related famous classical formulas. Method:Processing method of Pinelliae Rhizoma washed by hot water was established based on ancient Tangxi processing method， and the process conditions were optimized by single factor tests. The weight， moisture， ash， extract， total acid （calculated by succinic acid） contents and high performance liquid chromatography （HPLC） fingerprint of Pinelliae Rhizoma were compared before and after processing. In addition， the rabbit eye irritation test was conducted to evaluate the toxicity changes. Result:The processing method of Pinelliae Rhizoma washed by hot water was as following：washed by 4 times the amount of hot water at 80 ℃ for 10 times until clear water， transfused cross-section after incision， no or slight numbness in the mouth. The average moisture， ash， extract contents of Pinelliae Rhizoma washed by hot water were 9.34%， 1.71% and 4.22%， respectively. After being processed， the decline rates of weight and total acid content of Pinelliae Rhizoma were 7.49% and 43.31%. The HPLC fingerprint of Pinelliae Rhizoma before and after washing showed a decrease in all components， but there was no new chromatographic peak， and peak 9 （adenosine） reduced significantly. The results of rabbit eye irritation test showed that there was no obvious eye conjunctival irritation after washing， indicating that the toxicity of Pinelliae Rhizoma decreased obviously after washing. Conclusion:The established method of Pinelliae Rhizoma by Tangxi processing is stable and feasible， the aqueous extract of Pinelliae Rhizoma has no obvious eye conjunctival irritation after washing.

Eye irritation tests of polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a tissue model of reconstructed human cornea-like epithelium

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcular™ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.

Eye irritation tests of polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) using a tissue model of reconstructed human cornea-like epithelium

Disinfectants including polyhexamethylene guanidine phosphate (PHMG) and mixtures of chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT) have been widely used in Korea to prevent microbial growth in the humidifier water, which triggered an outbreak of serious respiratory diseases. In addition to the respiratory syndrome, disease-related symptoms including liver toxicity, asthma, and skin allergies were also found after extensive survey of people exposed to the humidifier disinfectants (HDs). In this study, eye irritation tests were performed based on the Organization for economic co-operation and development (OECD) test guidelines 492 using EpiOcular™ which is a tissue model of reconstructed human cornea-like epithelium. As results, the raw materials of PHMG (26% as active ingredient) and CMIT/MIT (1.5% as active ingredient) were classified under UN globally harmonized system of classification and labeling of chemical (GHS) category 1 or category 2. However, aqueous dilutions of raw materials such as market products of HDs that contain 0.13% of PHMG and 0.03% of CMIT/MIT or further dilutions of the market products for humidifier that contain 0.0013% of PHMG and 0.0003% of CMIT/MIT were classified under any category, which suggested absence of eye irritation at the test concentration.

Study on the Acute Eye Toxicity of PP1 Liposomes / 中国药师

Objective:To observe the acute toxic side effects of liposome PP 1 topically applied in eyes .Methods:PP1 liposomes (10, 60, 400 μmol· L-1 ) were used in one eye of SD rats , 4 times daily.The changes of conjunctiva , cornea and iris were observed under the slit-lamp biomicroscope , for three consecutive days , and evaluated by the stimulus score sheet of anterior segment .One week after the treatment , the corneas , irises and lenses were isolated , and their changes were observed under the light microscope .The ul-trastructural changes of corneal epithelial cells and endothelial cells were observed under the electron microscope .Results:There was a little of conjunctival secretion in one rat in the first day after the treatment with 400 μmol· L-1 PP1 liposomes, and the other rats were not irritant reaction .The corneal fluorescein staining of all rats were negative .The structures of cornea , iris, lens tissue were normal after given different concentrations of PP1 liposomes.Conclusion:PP1 liposomes at Low, medium and high concentrations show no a-cute eye toxicity in SD rats .

Evaluation of Eye Irritation Potential of Solid Substance with New 3D Reconstructed Human Cornea Model, MCTT HCE(TM)

The eye irritation potential of drug candidates or pharmaceutical ingredients should be evaluated if there is a possibility of ocular exposure. Traditionally, the ocular irritation has been evaluated by the rabbit Draize test. However, rabbit eyes are more sensitive to irritants than human eyes, therefore substantial level of false positives are unavoidable. To resolve this species difference, several three-dimensional human corneal epithelial (HCE) models have been developed as alternative eye irritation test methods. Recently, we introduced a new HCE model, MCTT HCETM which is reconstructed with non-transformed human corneal cells from limbal tissues. Here, we examined if MCTT HCETM can be employed to evaluate eye irritation potential of solid substances. Through optimization of washing method and exposure time, treatment time was established as 10 min and washing procedure was set up as 4 times of washing with 10 mL of PBS and shaking in 30 mL of PBS in a beaker. With the established eye irritation test protocol, 11 solid substances (5 non-irritants, 6 irritants) were evaluated which demonstrated an excellent predictive capacity (100% accuracy, 100% specificity and 100% sensitivity). We also compared the performance of our test method with rabbit Draize test results and in vitro cytotoxicity test with 2D human corneal epithelial cell lines.

Study Progress in Eye Irritation Test in vivo for Ophthalmic Preparations / 中国药师

Various new ophthalmic formulations have been prepared to enhance ocular bioavailability,while lots of irritant sub-stances are applied,including surfactants,polymers and other cationic materials. Therefore,safety of the preparations has been paid more and more attention besides the efficacy. Since in vitro experiments lack of associated enzymes and integral reaction of organiza-tion,the reasonability and correlation of the results extrapolated to the animal experiments still need to be further proved. The in vivo common eye irritation methods( winking,histopathological slices,Draize score and confocal microscopy test etc)were reviewed,eval-uated and analyzed in the paper.

Irritation of a new specimen preservation solution on the skin,eye of rabbits and its effect for specimens preser-vation / 局解手术学杂志

Objective To conduct the preliminary toxicology tests and evaluate the preservation effect on a new specimen preservation solution in order to provide scientific basis for its application security. Methods Twenty-four New Zealand white rabbits were randomly di-vided into the normal saline group, the formalin preservation group,the mixture group,and the new preservation solution group. Recorded the irritation of different solution on the skin,eye of rabbits,the effect of liver sample preservation in different solution,and the evaporation rate of these solution. And to find a set of preservative solution which is more suitable for preservation of specimens and can reduce the cost. Results The new preservation solution is stimulus on rabbit skin and eye,and it is stronger than the formaldehyde group. Compared with the other three groups,the mixture group has the best preservation effect, and the new preservation solution group has a better preservation effect than the formalin preservation solution group. Conclusion The 1∶1 mixture solution of the new preservation solution and formaldehyde is more suitable preservation solution and it can reduce the costs.

Clinical research on eye complications of acute chlorine poisoning / 国际眼科杂志(Guoji Yanke Zazhi)

?AlM:To observe the eye complications in the cases of acute chlorine gas poisoning. ?METHODS:A retrospective review of 121 cases of acute chlorine gas poising with eye irritation, dry eye and other eye complications in Linyi People’s Hospital from February 2009 to February 2013 was performed. ?RESULTS: Among 121 patients, 117 cases ( about 96. 7%) had complications of eye irritation and conjunctival and corneal epithelial damage, and the ocular surface damage was aggravated with the increasing level of chlorine gas poisoning. After 3, 6mo being discharged, 32 and 7 patients respectively occurred dry eye among 115 patients followed up. One mild chlorine poisoning patient, during the hormonotherapy of pulmonary complication, complicated with bullous retinal detachment, of which symptoms and physical signs had been improved after stopping hormonotherapy and adding drugs facilitating fluid absorption. One severe chlorine poisoning patient with loss of consciousness during the treatment, had corneal ulcer and after ulcer being healed with drug and conjunctival flap covering surgery, was left permanent leukoma cornea. ?CONCLUSlON: Acute chlorine poisoning can cause corneal and conjunctival epithelial damage and dry eye. Ocular complications like bullous retinal detachment associated with hormone application should be paid more attention to in the hormonotherapy. For some patients with severe poisoning, the therapy of corneal and conjunctival epitheliums should be taken seriously in case of irreparable damage in rescuing patient’s life.

Integrated CAMVA and BCOP methods to predict eye irritation caused by cosmetics / 中国比较医学杂志

Objective To explore the use of integrated two methods in vitro in prediction of eye irritation caused by cosmetics.Method Chorioallantoic membrane vascular assay ( CAMVA), bovine corneal opacity and permeability (BCOP) and Draize rabbit eye irritation test were used to determine the predictive potential of eye irritation of 60 kinds of cosmetics.Results CAMVA method was able to distinguish 41 non-irritant samples and 18 irritant samples.BCOP method was able to predict 35 non-irritant samples , 21 mild-moderate irritant samples and 4 severe irritant samples . Combination of CAMVA and BCOP methods could obviously improve the identification ability of irritation , and the classification consistency with Draize rabbit eye irritation testing reached 98.3%.Conclusions The integrated test strategy combined BCOP with CAMVA can be used to appropriately predict ocular irritation of cosmetics , with a prediction range covering non-irritant to severe irritant samples .

Determination of eye irritation potential of low-irritant products: comparison of in vitro results with the in vivo draize rabbit test

In an attempt to build the evaluation strategies to assess the human eye irritation, a reassessment of some in vitro tests is necessary, particularly concerning the non-irritants, mild and moderate irritants. Thus, the correlations between results obtained from the Draize test with the in vitro methods HET-CAM (Hens Egg Test-Chorion Allantonic Membrane) and RBC haemolysis assay to assess the ocular irritancy potential of 20 eye drops were examined. Parameters such as accuracy (%) and specificity (%) were determined. All results were correlated with RBC correctly with the results obtained in the Draize test. The HET-CAM presented four false-positive results, showing a tendency of data overestimation. Despite the high specificity provided mainly by the RBC, it would be necessary to test a wider range of products representing all the scales of irritation to confirm its ability to be used as a first alternative to test products that could be presumptive non-irritants.

Perfil de tolerancia ocular de un cosmético para bebe in vivo / Ocular tolerance profile of a cosmetic product for babies in vivo

Introducción: el estudio realizado previo al mercadeo de un cosmético para satisfacer la necesidad de obtener el registro sanitario, contribuye a garantizar su seguridad y eficacia para prevenir un problema de salud pública. Objetivo: describir el riesgo ocular latente por un champú mediante pruebas in vivo. Métodos: se realizó un estudio clínico hermenéutico y reflexivo, bajo la observación directa macroscópica en términos de efectos clínicos; determinación de los efectos promedios en 6 conejos mediante la escala de valores según la OCDE y estudio histopatológico de una muestra de tejido del ojo. Resultados: el 50 % de los animales mostraron el nivel 1 de lesión ocular; el 16,67 % el nivel 2 y el 33,33 % el nivel 3. Ninguno de los animales mostró el nivel 4 (lesión máxima). El análisis del promedio de los efectos clínicos y el análisis histopatológico confirman la sensibilidad del conejo como referente experimental aplicable para los bebés. Conclusiones: el champú podría producir efectos oculares leves, pero el posible riesgo ocular debe ser advertido hasta que no se demuestre su inocuidad.

Introduction: the study that is performed for health registration before marketing any cosmetic product assures its safety and efficacy to prevent a public health problem. Objective: to describe the possible eye risk caused by a shampoo for babies through in vivo testing. Methods: a clinical exploratory and hermeneutic study based on direct macroscopic observation of clinical effects; determination of average effects in 6 rabbits by the OECD value scale and a histopathological study of a sample of eye tissue. Results: fifty percent of rabbits showed level 1 ocular injury; 16.67 % suffered level 2 whereas 33.33 % had level 3. None of the animals reached level 4 (maximum level in injuries). The analysis of the average clinical effects and the histopathological study confirmed the sensitivity of the rabbit as experimental reference that may be applicable to babies. Conclusions: the shampoo might cause mild eye effects; however the possible ocular risk must be stated until such time as the safety of the product is proven.

Evaluation of Caffeine Gels on Physicochemical Characteristics and In Vivo Efficacy in Reducing Puffy Eyes.

The eyelids are the thinnest skin in the body, leading to be easy for the blood vessels to show through the skin caused a swollen and dark appearance called puffy eyes. Placing refrigerated damp tea bags on the eyelids has been believed for a long time that it can reduce the puffy eyes due to the vasoconstriction of caffeine. This study aimed to characterize physicochemical properties and to determine in vivo efficacy in reducing puffy eyes of the prepared caffeine gels. The formulation composed of 3% caffeine, 2% ethanol, 0.3% Uniphen® P-23, 7.5% propylene glycol, 0.5% Carbopol® Ultrez-21 and water to 100% was selected for eye irritation test and efficacy evaluation since it possessed good characteristics and provided sustained skin permeation. The 34 volunteers (18 women, 16 men) who easily developed puffy eyes after going to bed without sleep and with no irritation to caffeine gel as well as its gel base were treated with the gels in a randomized, double-blind, placebo-controlled trial. The skin permeation profiles showed that all caffeine gels allowed caffeine to permeate through the newborn pig skin. However, the overall efficacy of the selected caffeine gel in reducing puffy eyes was not significantly different from that of its gel base. It could be concluded that the cooling effect of the hydrophilic gels was the main parameter in reduction of eye puffiness rather than the vasoconstriction of caffeine.

Acute eye irritation study of a mixture of glyphosate isopropylamine salt and 2,4 D-isopropylamine.

This is an acute irritation study of the eye of a mixture of herbicides containing 240 g/l of glyphosate isopropylamine and 2,4 D-isopropylamine in the rabbits. This study was conducted according the methods as dercribed by the United States Environmental Protection Agency (EPA). Our results show that the combination of the herbicides causes mild conjunctivitis, mild chemosis, eye discharge and corneal injury. The ocular alteration, however, was reversible in nature.

Toxicological study of the molluscicidal latex of Euphorbia splendens: irritant action on skin and eye

Aqueous solutions of the molluscicidal latex of Euphorbia splendens are irritant to the rabbit eye in concentrations higher than 0.35% and to the rabbit skin in concentrations higher than 0.5%. Although this irritant potential does not proclude its use as a molluscicide, special precautions are recommended for hanbdling and application of the product and the hazard of skin tumor-promoting potencial should be carefully investigated before its use for schistosomiasis vector control.