Severe Eye Irritation Research Articles

Bis-(2-Chloroisopropyl) ether.

Bis-(2-Chloroisopropyl) ether (BCIPE) was used as a solvent for fats, greases, paint, varnish removers, and in spotting and cleaning solutions. However, BCIPE has not been commercially manufactured or used for numerous years. In experimental animal studies, BCIPE is moderately toxic following acute oral, dermal, and inhalation routes of exposure. BCIPE is a severe eye irritant but not a dermal irritant or dermal sensitizer. BCIPE was not genotoxic or mutagenic in in vitro and in vivo assays; it was not toxic in a 3-generation reproductive dietary study in rats. Short-term, repeated inhalation and oral exposure in rats produced increased liver and kidney weights and congestion; dermal exposure in rabbits did not produce any observable adverse effects. BCIPE did not produce a statistically significant increase in tumors in two different 2-year dietary studies in mice and rats. In mice, technical grade BCIPE produced increased incidences of alveolar/bronchiolar adenomas in females, hepatocellular carcinomas in males, and a low incidence of forestomach hyperplasia (in both sexes at the high-dose). Further investigation with technical grade BCIPE concluded that these effects were species- and dose-specific with limited, if any, relevance to humans. The NOAEL of 400 ppm (15 mg/kg/day) from the 2-year dietary study in female rats was considered the point of departure for the health-based WEEL derivation. After adjustment for duration of exposure, interindividual variability, and intraindividual variability, an 8-h time-weighted average (TWA) WEEL value of 3 ppm (21 mg/m3) was derived. This exposure limit is expected to provide a significant margin of safety against any potential adverse health effects in workers.

Differences in prescribed medicinal cannabis use by cannabinoid product composition: Findings from the cannabis as medicine survey 2020 (CAMS-20) Australia-wide study.

Prescribed medicinal cannabis (MC) is an increasingly common prescription in Australia for treating pain, anxiety, and sleep disorders. Prescribed MC products generally contain tetrahydrocannabinol (THC) and/or cannabidiol (CBD) in a variety of dose levels and forms. It is unclear whether THC and CBD products are used by patients with different characteristics and for different conditions. To examine consumer experiences of using THC- and CBD-containing prescribed MC products to better understand how they are being used within the Australian context. We utilised data collected from an online anonymous cross-sectional survey of individuals (CAMS-20 survey), consisting of Australian residents using cannabis for therapeutic reasons. We focused on a subgroup of participants (N = 546) receiving prescribed MC products. We utilised linear, logistic, and multinomial regression modelling to analyse responses to survey questions based on the cannabinoid profile of the prescribed product. Participants prescribed THC-dominant MC products were statistically more likely to be younger, male, and to prefer inhaled routes of administration than participants using CBD-dominant products who were older, female, and preferred oral routes of administration. Pain and mental health were the most common reasons for all types of prescribed MC, but were more likely to be treated with THC than CBD despite the significantly higher risk of mild to severe drowsiness, dry mouth and eye irritation. Consumer reported effectiveness of prescribed MC was very positive, particularly for THC-containing products. Consumers on opioids and antipsychotics were statistically more likely to be prescribed THC-containing products than products containing CBD only, despite the greater risk of impairment. This Australia-wide study found clear differences in consumer-reported experiences of prescribed THC- and CBD-containing products. Current prescriptions of these products do not always align with relevant clinical guidance. Educating prescribers around cannabinoid products is essential to ensure optimal prescribing practices and to prevent avoidable drug side effects and interactions.

Ptosis in long standing VKC in young adults

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. Though medically treated, some complications of the disease like ptosis may require surgical intervention, thus identifying the association of ptosis with VKC is of utmost importance. This study was done to see the relation between long-standing VKC and acquired ptosis in young adults.This was a hospital based non-comparative, observational study, conducted in the department of Ophthalmology, SKIMS Medical College Hospital, and Srinagar from March 2020 to May 2022. 60 patients upto the age of 40 years with any form of VKC were included in the study. Ocular examination included visual acuity testing, slit lamp biomicroscopic examination to evaluate corneal and conjunctival involvement, proper history and evaluation of ptosis.Mean age of cases was 16.23± 6.97. Out of 60 patients maximum were in the age group of 10-15 years (31.66%), followed by the age group of 15-20 years (21.66%). Out of total 60 cases 46(76.66%) were male and 14(23.33%) were female. Palpebral form of the disease was seen to be in most of the cases 53.33%, followed by mixed form of the disease in 28.33% and bulbar disease in 18.33% of the cases. Presence of acquired ptosis as a complication due to VKC was seen in 9(15%) patients. Out of these 9 patients 7 patients presented with unilateral ptosis and 2 patients presented with bilateral ptosis. Average duration of symptoms in these patients was 5.0±1.8 years, indicating that ptosis is a complication of long standing VKC. All these patients had palpebral or mixed form of VKC, none had bulbar form of the disease.Our study revealed that prolonged severe VKC may induce a lower position of the upper eyelid and eventually lead to ptosis, which is a non-reversible complication of VKC and requires surgical correction. Thus better primary eye care for the management of VKC in children may prevent this complication.

Sphingolipidomics of Bovine Pink Eye: A Pilot Study.

Simple SummaryThe liquid tear film, which protects the eye from the environment, is a dynamic fluid containing a large number of complex lipids. Disruptions of these lipids by infections can result in damage to the eye and ultimately blindness. In this study we characterized various lipid subfamilies present in the tear film of the eye and the effect of pink eye infections in cattle. Our findings demonstrate that the pink eye infections dramatically decrease the levels of lipids in the tear film covering the eye and suggest that this is a major factor in the development of blindness in infected cattle.Sphingolipids are essential structural components of tear film that protect the surface of the eye from dehydration. A detailed analysis of the effects of pink eye infections on the sphingolipidome in cattle has not previously been undertaken. We recently published a new assay utilizing high-resolution mass spectrometric monitoring of the chloride adducts of sphingolipids that provides enhanced sensitivity and specificity. Utilizing this assay, we monitored decreases in the levels of tear film ceramides with short-chain fatty acids, hydroxy-ceramides, phytoceramides, and hydroxy-phytoceramides. Dihydroceramide levels were unaltered and increased levels of ceramides with long-chain fatty acids (24:0 and 24:1) were monitored in cattle with pink eye. The data from this pilot study (n = 8 controls and 8 pink eye) demonstrate a major disruption of the lipid tear film layer in pink eye disease, that can result in severe eye irritation and damage.

Toxicity assessment of emamectin benzoate and its commercially available formulations in Pakistan by in vivo and in vitro assays

Emamectin benzoate (EMB) is generally considered a safe insecticide in agriculture and veterinary practices, yet, it can cause cytotoxic and genotoxic effects. Hence, the aim of this study was to evaluate toxic effects of 80% EMB and its commercially used formulations (Tycon 1.9% EC and Tycon plus 5% EW) in Pakistan and tested for acute toxicity in albino rats, rabbits and fish (Labeo rohita). Genotoxicity was investigated by in vivo comet assay and bone marrow micronucleues test in the rats. In vitro mutagenicity was tested in Salmonella typhimurium TA98 and TA100. The tested EMB formulations were found moderately toxic (oral LD50: 122–168 mg/kg), causing severe eye irritation in rabbits, highly toxic to fish (LC50: 9–43 μg/L) and found non mutagenic. Oral administrations of EMB (80% and 5%) at 100 mg/kg of body weight to male rats reduced red blood cells, hemoglobin, and slightly increased the blood glucose, urea and liver enzymes levels but had no significant damage to DNA. EMB induced bone marrow toxicity was observed as reduction of polychromatic erythrocytes. Overall, EMB exposure was highly toxic to fish, and caused hemo- and hepatotoxicity in rats. These findings warrant cautious use of EMB formulations in agrochemicals and veterinary medicine.

Synthesis of V Doped Ca Bismuthate Nanoflakes for Photocatalytic Removal of Crystal Violet Dye

Background: Crystal Violet Dye (CV) can cause severe eye irritation and cancer due to its adsorption, ingestion, and inhalation effect. Therefore, CV in wastewater systems poses as a severe risk to human health and the environment. It is essential to remove CV before CV is discharged in the environment. Methods: Vanadium doped calcium bismuthate nanoflakes with the vanadium mass ratio of 1 wt%, 3 wt.%, 5 wt.%, and 10 wt.% have been synthesized by a simple hydrothermal route using sodium vanadate as a vanadium raw material. The obtained vanadium doped calcium bismuthate products were analyzed by X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and solid diffuse reflection spectrum. Results: XRD patterns show that the vanadium in the doped nanoflakes exists as triclinic Bi3.5V1.2O8.25 and monoclinic Ca0.17V2O5 phases. SEM observations show that the morphology of the products is closely related to the vanadium mass ratio. The morphology changes from the nanoflakes to irregular nanoparticles is observed by increasing the vanadium mass ratio. The bandgap of the nanoflakes decreases to 1.46 eV and 1.01 eV when the doped vanadium mass ratio reaches 5 wt.% and 10 wt.%, respectively. The photocatalytic performance for the CV removal can be greatly enhanced using 5 wt.% and 10 wt.% vanadium doped calcium bismuthate nanoflakes, respectively. By increasing the irradiation time, vanadium mass ratio, and dosage of the nanoflakes, the photocatalytic activity for the CV removal can be improved. Conclusion: 10 wt.% vanadium doped calcium bismuthate nanoflakes have the best photocatalytic performance for CV removal. Vanadium-doped calcium bismuthate nanoflakes exhibit great application potential for the removal of organic pollutants.

Novel polypyrrole-carbon black doped ZnO nanocomposite for efficient amperometric detection of hydroquinone

Long-term exposure to hydroquinone (HQ) results in severe eye irritation and sometimes can lead to impaired vision. Therefore, we have proposed a novel electrochemical sensor for efficient detection of HQ using a new polypyrrole/carbon black doped ZnO nanocomposite (PPy/CB/ZnO NC) fabricated glassy carbon electrode (GCE). The structure and morphology of PPy/CB/ZnO active material were investigated using FE-SEM, TEM, EDS, XRD, FTIR, and Raman spectroscopy. With a high sensitivity of 0.5405 μAμM−1cm−2 and an ultra-low limit of detection (LOD) of 22.9 ± 0.1 nM, this innovative electrochemical hydroquinone sensor can determine a wide range of HQ from 0.9 μM to 6.5 mM in neutral pH. This newly developed HQ sensor was also applied to detect potential chemical interfering species. The proposed HQ sensor demonstrated highly acceptable results in real sample analysis using the standard addition method. During the electrochemical detection of HQ, this novel PPy/CB/ZnO/GCE assembly showed exceptional reproducibility, repeatability and stability. Therefore, this approach will be an efficient technique to develop a selective and sensitive electrochemical sensor in detecting hazardous phenolic derivatives for the green environment.

Safety and efficacy of STABILFLOR® as a zootechnical feed additive for pigs for fattening.

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of STABILFLOR ® (zinc ethylenediaminetetraacetic acid (Zn‐EDTA) and copper diammonium EDTA (Cu‐EDTA) dried on chicory pulp and supplemented with zinc oxide and copper oxide), as a zootechnical additive for pigs. STABILFLOR ® is intended to be used in feed for pigs for fattening at a minimum and maximum levels of 500 and 1,000 mg/kg complete feed, respectively. The Panel could not conclude on the safety of STABILFLOR ® for pigs for fattening owing to the lack of adequate data. At the proposed used levels in feed the additive may exert antimicrobial activity in the gut microbiota. The use of the additive resulted neither in residues of Zn‐EDTA, Cu‐EDTA or EDTA nor on an increase in total zinc and copper deposition in edible tissues; Zn‐EDTA and Cu‐EDTA had not a genotoxic potential; the Panel concluded that STABILFLOR ® at 1,000 mg/kg complete feed for pigs does not pose any concern to the safety of consumers. The handling of STABILFLOR ® will lead to a copper exposure of the users that poses a risk by inhalation; the additive is not a skin irritant or a skin sensitiser but is a severe eye irritant. Regarding environmental safety, no concern was expected for the terrestrial compartment. A risk for groundwater was highlighted for Zn‐EDTA. Due to the absence of data, the risk for the aquatic compartment could not be assessed. Only one efficacy study showed positive effects of STABILFLOR ® in pigs for fattening at 1,000 mg/kg complete feed; a conclusion on the efficacy of STABILFLOR ® could not be drawn. The minimum use level of 500 mg STABILFLOR ®/kg complete feed was not tested.

Safety and efficacy of VevoVitall® (benzoic acid) as feed additive for pigs for fattening.

The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of VevoVitall® (benzoic acid) as a zootechnical feed additive for pigs for fattening. The additive is currently authorised for pigs for fattening with the effect of ‘urinary pH decrease’ at the minimum and maximum use of 5,000 and 10,000 mg/kg complete feed, respectively. The current application intends to support the use of the additive with the specific effect of ‘improvement of performance parameters’ at the minimum dose of 3,000 mg additive/kg complete feed, and keeping the same other conditions as for the use already authorised. The FEEDAP Panel assessed already the safety of the product when used in pigs for fattening in 2007 and 2017. The Panel confirms its former assessments that VevoVitall® used as a feed additive in pigs for fattening at the maximum level of 10,000 mg/kg is considered as safe for pigs for fattening, consumers of food derived from pigs fed the additive and the environment. VevoVitall® does not pose a risk by inhalation to users and is not a skin sensitiser but is a skin irritant and a severe eye irritant. Based on the results of three efficacy studies, the FEEDAP Panel concluded that VevoVitall® has the potential to increase the performance in pigs for fattening at the level of 3,000 mg/kg complete feed.

Evaluation of a tiered in vitro testing strategy for assessing the ocular and dermal irritation/corrosion potential of pharmaceutical compounds for worker safety

Introduction: Irritation reactions are a frequently reported occupational illness. The potential adverse effects of pharmaceutical compounds (PCs) on eye and skin can now be assessed using validated in vitro methods.Objectives: Our overall aim is to reduce animal testing by replacing the historically utilized in vivo test methods with validated in vitro test methods which accurately determine the ocular and dermal irritation/corrosion potential of PCs to inform worker safety within the pharmaceutical space. Bristol–Myers Squibb (BMS) and the Institute for In Vitro Sciences (IIVS) have therefore conceptualized and internally qualified a tiered in vitro testing strategy to inform occupational hazards regarding eye and skin irritation and corrosivity of PCs. For the small scale pre-qualification phase, we paired historical in vivo and newly generated in vitro data for 15 PCs to determine the predictive capacity of in vitro assays already validated for the eye and skin irritation/corrosion endpoints and accepted for certain regulatory submissions. During the post-qualification phase, a group of 24 PCs were subjected exclusively to the developed tiered testing strategy, which is based on three Organisation for Economic Co-operation and Development (OECD) in vitro methods.Materials and methods: The qualified in vitro testing strategy utilizes the Corrositex® assay for the corrosivity (OECD TG 435), the Bovine Corneal Opacity and Permeability (BCOP) assay for ocular irritation (OECD TG 437), and the EpiDerm™ tissue model-based Skin Irritation Test (SIT) for dermal irritation (OECD TG 439). In the first step, the pH of each PC was determined. For compounds with pH extremes ≥11 or ≤2, the Corrositex® assay was generally conducted first. For compound(s) that were incompatible with or were negative in the Corrositex® assay or had pH values between 2 and 11, the BCOP assay and SIT were performed first.Results: The results of the tiered testing strategy’s qualification phase demonstrated that the BCOP assay is sensitive enough to identify a wide range of eye irritation/corrosion potentials and its over-prediction rate was considered acceptable to inform occupational hazards and ensure the proper handling practices of PCs. The SIT correctly predicted the skin irritation potential of 14 out of the 15 PCs included in the qualification phase, only over-predicting one PC. In the post-qualification phase, four PCs out of four tested were predicted corrosive by the Corrositex® assay and thus no further testing was needed or conducted. The rest of the PCs were evaluated in the BCOP assay (both neat and as a 20% dilution), with the higher response being used for hazard classification. Four PCs were determined to be severe eye irritants, 1 a moderate irritant, 8 were mild irritants, and 8 were non-irritants. The same set of PCs was evaluated using the SIT and were classified as non-irritants to skin. These results are consistent with the BMS historical in vivo results showing a very low number of PCs as skin irritants.Conclusions: This tiered in vitro testing strategy, which replaces the use of animal studies, was found to be reasonably accurate in its predictive capacity when compared to historical in vivo results and represents a conservative and reliable platform that can be utilized for the prediction of ocular and dermal irritation/corrosion potential of PCs and for subsequent GHS classification and worker safety hazard communications.

Assessment of the application for renewal of authorisation of VevoVitall® (benzoic acid) as feed additive for weaned piglets and pigs for fattening.

VevoVitall® is a feed additive consisting of benzoic acid. It is currently authorised as a zootechnical additive for weaned piglets and pigs for fattening. This opinion concerns the renewal of the authorisation of benzoic acid as a zootechnical additive in feed. In 2005 and 2017, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) adopted two opinions on the safety and efficacy of VevoVitall® as a feed additive for weaned piglets and pigs for fattening, respectively. The applicant has provided data demonstrating that the additive currently in the market complies with the conditions of authorisation. Furthermore, according to the information provided in the technical dossier, no new evidence has been identified that would make the FEEDAP Panel reconsidering the previous conclusions on the safety of the additive. The Panel confirms that the additive is safe at the maximum authorised concentrations of 5,000 and 10,000 mg/kg feed for weaned piglets and pigs for fattening, respectively; a margin of safety cannot be determined for weaned piglets while a margin of safety of less than 1.5 is established for pigs for fattening. The use of VevoVitall® in feeds for weaned piglets and pigs for fattening at the maximum authorised concentrations does not pose any safety concern for consumers and the environment. The use of VevoVitall® does not pose a risk by inhalation to users and is not a skin sensitiser. The new available data confirm that the additive is a skin irritant and a severe eye irritant. A recommendation concerning the potential toluene residues in the additive has been posted.

Safety and efficacy of VevoVitall® (benzoic acid) as feed additive for minor porcine species.

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on VevoVitall® (benzoic acid) as a feed additive for minor porcine species, when used as zootechnical additive at a maximum level of 5,000 mg/kg complete feed. The safety and efficacy of the additive had been evaluated by the FEEDAP Panel on weaned piglets (at the maximum supplementation level of 5,000 mg/kg complete feed) and pigs for fattening and pigs for reproduction (at the maximum level of 10,000 mg/kg complete feed). Subsequent to EFSA's assessments, the additive has been authorised for use in feed of weaned piglets, pigs for fattening and sows. To the knowledge of the FEEDAP Panel, there was no new information that might modify its previous assessments on VevoVitall® concerning safety for consumers and the environment; therefore, this opinion focused only on the safety of the target animals and the efficacy of the product. The FEEDAP Panel concluded that VevoVitall® is safe at the supplementation level of 5,000 mg/kg complete feed for minor porcine species for fattening and for reproduction; the FEEDAP could not conclude on the safety of the additive for weaned minor porcine species. VevoVitall® does not represent a risk for the consumer and the environment. VevoVitall® does not pose a risk by inhalation to users and is not skin sensitiser, but is a skin irritant and a severe eye irritant. VevoVitall® has the potential to decrease the urinary pH in minor porcine species at the dose of 5,000 mg/kg complete feed. A remark on the relevance of the claim has been posted by the Panel.

Eye irritation potential: palm-based methyl ester sulphonates

Aim: To evaluate eye irritation potential of palm-based methyl ester sulphonates (MES) of different chain lengths; C12, C14, C16, C16:18.Methods: The Bovine Corneal Opacity and Permeability test method (BCOP), OECD Test Guideline 437, was used as an initial step to study the inducing effect of palm-based MES on irreversible eye damage. The second assessment involved the use of reconstructed human corneal-like epithelium test method, OECD Test Guideline 492 using SkinEthic™ Human Corneal Epithelium to study the potential effect of palm-based MES on eye irritancy. The palm-based MES were prepared in 10% solution (w/v) in deionized water and tested as a liquid and surfactant test substances whereby both test conducted according to the liquid/surfactant treatment protocol.Results: The preliminary BCOP results showed that palm-based MES; C12, C14, C16, C16:18 were not classified as severe eye irritants test substances with in vitro irritancy score between 3 and the threshold level of 55. The second evaluation using SkinEthic™ HCE model showed that palm-based MES; C12, C14, C16, C16:18 and three commercial samples were potentially irritants to the eyes with mean tissue viability ≤ 60% and classified as Category 2 according to United Nations Globally Harmonized System of Classification and Labelling of Chemicals. However, there are some limitations of the proposed ocular irritation classification of palm-based MES due to insolubility of long chain MES in 10% solution (w/v) in deionized water.Conclusion: Therefore, future studies to clarify the eye irritation potential of the palm-based MES will be needed, and could include; methods to improve the test substance solubility, use of test protocol for solids, and/or inclusion of a benchmark anionic surfactant, such as sodium dodecyl sulphate within the study design.

Analysis of Draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data.

SummaryPublic data from ECHA online dossiers on 9,801 substances encompassing 326,749 experimental key studies and additional information on classification and labeling were made computable. Eye irritation hazard, for which the rabbit Draize eye test still represents the reference method, was analyzed. Dossiers contained 9,782 Draize eye studies on 3,420 unique substances, indicating frequent retesting of substances. This allowed assessment of the test’s reproducibility based on all substances tested more than once. There was a 10% chance of a non-irritant evaluation after a prior severe-irritant result according to UN GHS classification criteria. The most reproducible outcomes were the results negative (94% reproducible) and severe eye irritant (73% reproducible).To evaluate whether other GHS categorizations predict eye irritation, we built a dataset of 5,629 substances (1,931 “irritant” and 3,698 “non-irritant”). The two best decision trees with up to three other GHS classifications resulted in balanced accuracies of 68% and 73%, i.e., in the rank order of the Draize rabbit eye test itself, but both use inhalation toxicity data (“May cause respiratory irritation”), which is not typically available.Next, a dataset of 929 substances with at least one Draize study was mapped to PubChem to compute chemical similarity using 2D conformational fingerprints and Tanimoto similarity. Using a minimum similarity of 0.7 and simple classification by the closest chemical neighbor resulted in balanced accuracy from 73% over 737 substances to 100% at a threshold of 0.975 over 41 substances. This represents a strong support of read-across and (Q)SAR approaches in this area.

Through-bond energy transfer-based ratiometric two-photon probe for fluorescent imaging of Pd(2+) ions in living cells and tissues.

Palladium can cause severe skin and eye irritation once it enters the human body. Ratiometric two-photon fluorescent probes can both eliminate interference from environmental factors and realize deep-tissue imaging with improved spatial localization. To quantitatively track Pd(2+) in biosystems, we report here a colorimetric and two-photon ratiometric fluorescent probe, termed Np-Rh-Pd, which consists of a two-photon fluorophore (naphthalene derivative with a D-π-A structure) and a rhodamine B dye. The two fluorophores are directly linked to form a two-photon ratiometric fluorescent probe for Pd(2+) based on a through-bond energy transfer (TBET) strategy. It exhibits highly efficient energy transfer (90%) with two well-resolved emission peaks (wavelength difference of 100 nm), which could efficiently diminish the cross talk between channels and is especially favorable for ratiometric bioimaging applications. A signal-to-background ratio of 31.2 was observed for the probe, which affords a high sensitivity for Pd(2+) with a detection limit of 2.3 × 10(-7) M. It was also found that acidity does not affect the fluorescent response of the probe to Pd(2+), which is favorable for its applications in practical samples. The probe was further used for fluorescence imaging of Pd(2+) ions in live cells and tissue slices under two-photon excitation, which showed significant tissue-imaging depths (90-270 μm) and a high resolution for ratiometric imaging.

Evaluating Systemic Toxicity in Rabbits after Acute Ocular Exposure to Irritant Chemicals

Acute systemic toxicity via ocular exposure route is not a well understood aspect. Any material/drug/chemical that comes in contact with the eye can evade the first pass metabolism and enter the systemic circulation through the conjunctival blood vessels or via the nasolacrimal route. In this study, the effect of ocular irritant chemicals on the systemic toxicity was assessed in rabbit. Eyes of rabbits were exposed to known ocular irritant (cetyl pyridinium chloride, sodium salicylate, imidazole, acetaminophen, and nicotinamide) for 24 h and scored. After a period of 72 h, blood was collected from the animals for examining the hematological and biochemical parameters. The animals were then sacrificed and the eyes were collected for histopathology and cytokine analysis by ELISA. Splenocyte proliferation was assessed by tritiated thymidine incorporation assay. The liver and brain of the treated animals were retrieved for evaluating oxidative damage. The chemicals showed moderate to severe eye irritation. Inflammation was not evident in the histopathology but proinflammatory markers were significantly high. The splenocyte proliferation capacity was undeterred. And there was minimal oxidative stress in the brain and liver. In conclusion, acute exposure of ocular irritants was incapable of producing a prominent systemic side effect in the current scenario.

Vernal keratoconjunctivitis: A severe allergic eye disease with remodeling changes

Vernal keratoconjunctivitis (VKC) is an unusually severe sight-threatening allergic eye disease, occurring mainly in children. Conventional therapy for allergic conjunctivitis is generally not adequate for VKC. Pediatricians and allergists are often not familiar with the severe clinical symptoms and signs of VKC. As untreated VKC can lead to permanent visual loss, pediatric allergists should be aware of the management and therapeutic options for this disease to allow patients to enter clinical remission with the least side effects and sequelae. Children with VKC present with severe ocular symptoms, that is, severe eye itching and irritation, constant tearing, red eye, eye discharge, and photophobia. On examination, giant papillae are frequently observed on the upper tarsal conjunctiva (cobblestoning appearance), with some developing gelatinous infiltrations around the limbus surrounding the cornea (Horner-Trantas dot). Conjunctival injections are mostly severe with thick mucus ropy discharge. Eosinophils are the predominant cells found in the tears and eye discharge. Common therapies include topical antihistamines and dual-acting agents, such as lodoxamide and olopatadine. These are infrequently sufficient and topical corticosteroids are often required for the treatment of flare ups. Ocular surface remodeling leads to severe suffering and complications, such as corneal ulcers/scars. Other complications include side effects from chronic topical steroids use, such as increased intraocular pressure, glaucoma, cataract and infections. Alternative therapies for VKC include immunomodulators, such as cyclosporine A and tacrolimus. Surgery is reserved for those with complications and should be handled by ophthalmologists with special expertise. Newer research on the pathogenesis of VKC is reviewed in this article. Vernal keratoconjunctivitis is a very important allergic eye disease in children. Complications and remodeling changes are unique and can lead to blindness. Understanding of pathogenesis of VKC may lead to better therapy for these unfortunate patients.

Improvement of the Bovine Corneal Opacity and Permeability (BCOP) assay as an in vitro alternative to the Draize rabbit eye irritation test

Measurement of ocular irritancy is a necessary step in the safety evaluation of both industrial and consumer products. Assessment of the acute eye irritation potential is therefore part of the international regulatory requirements for testing of chemicals.The Bovine Corneal Opacity and Permeability (BCOP) assay is generally accepted as a valid in vitro alternative method to the Draize eye irritation test to detect corrosive and severe eye irritants (category 1), but has not proven sensitive enough to discriminate accurately moderate (category 2A/2B) to mild and non-irritating compounds. In the currently accepted BCOP assay, opacity is determined by the amount of light transmission through the cornea, and permeability is determined by the amount of sodium fluorescein dye that passes through all corneal cell layers. Both measurements are used to assign an In Vitro Irritancy Score (IVIS) for prediction of the in vivo ocular irritation potential of a test substance. Nowadays, opacity is measured by an OP-KIT opacitometer providing a center-weighted reading of light transmission by measuring changes in voltage when the transmission of white light passes through the cornea alters. As a consequence, this may underestimate opacity that develops as spots or heterogeneous opaque areas on the periphery of an isolated cornea.A prototype of a laser light-based opacitometer (PLLBO) allowing better measurement of opacities was developed by Van Goethem et al. (2010). This new device showed improved sensitivity to detect subtle changes in corneal transparency. Furthermore, the new opacitometer allowed the analysis of the complete corneal surface and was able to detect more efficiently opaque spots located along the sides of the excised corneas.A further improved prototype of the PLLBO was constructed in combination with a camera and a speckle noise reducer. Treatment conditions of the corneas in the cornea holders were optimized in order to mimic more the real in vivo situation. A set of test compounds with irritancy potencies especially in the mild and moderate range was tested. The improved LLBO showed some promising features which potentially could improve the usefulness of the BCOP test. Adaptation of cornea holders showed to be of limited value and only restricted to concentrations up to 15% which mimics more test conditions in industry.This 3-year research project was sponsored by the Stavros Niarchos Foundation (Greece).

Screening for potential hazard effects from four nitramines on human eye and skin

Amines have potential to be used in CO2 capture and storage (CCS) technology, but as they can be released into the environment and be degraded into more toxic compounds, such as nitrosamines and nitramines, there have been concerns about their negative impact on human health. We investigated the potential toxic effects from acute exposure to dimethylnitramine (DMA–NO2), methylnitramine (MA-NO2), ethanolnitramine (MEA-NO2) and 2-methyl-2-(nitroamino)-1-propanol (AMP-NO2). The eye irritation, and skin sensitization, irritation and corrosion potential of these substances have been evaluated in vitro using the Bovine Corneal Opacity and Permeability (BCOP) assay, VITOSENS® assay, Reconstructed Human Epidermis (RHE) skin irritation test and Corrositex Skin corrosion test, respectively. Exposure to DMA–NO2 induced a mild eye irritation response, while MA-NO2, MEA-NO2 and AMP-NO2 were shown to be very severe eye irritants. MA-NO2 and MEA-NO2 were tested for skin sensitization and found to be non-sensitizers to the skin. In addition, none of the four test substances was irritant or corrosive to the skin.

Assessing the Genotoxic Potential of Chlorothalonil Drift from Potato Fields in Prince Edward Island, Canada

Chlorothalonil, a broad-spectrum nonsystemic foliar fungicide, is one of the most extensively used pesticide active ingredients on Prince Edward Island, Canada, for blight control on potatoes. In ambient air-sampling programs conducted in 1998 and 1999 and from 2002 to 2004, chlorothalonil was measured in 97% of air samples collected. It is known to produce severe eye and skin irritation, is cytogenic and is considered a possible human carcinogen by the United States Environmental Protection Agency and the International Agency for Research on Cancer. Inhalation studies that quantify chlorothalonil subchronic effects (e.g., genotoxicity) are lacking. The purpose of this study was to assess the possible genotoxic potential of chlorothalonil under field conditions by using the alkaline comet assay to assess DNA damage in CD-1 mice. Mice were selected as a surrogate species for wild small mammals (e.g., meadow voles, deer mice) known to inhabit areas adjacent to potato fields. Mice were placed at three locations downwind of a chlorothalonil application (0, 30, and 100 m) and at one up-wind control location at least 30 m from the field. Downwind mice were exposed to drift throughout the spray period (approximately 30 min) and for an additional hour after spraying. Air samples were collected during the spray trials (before, during, and after spraying) using high-volume polyurethane foam and PM(2.5) air samplers. Pesticide deposits were measured using 20 × 25 cm glass-fibre filters. After exposure, blood was collected from each mouse, and DNA strand breaks in white blood cells measured using comet assay. Results suggest that metrics of DNA damage [tail length (TL), percent DNA in tail] were not significantly related to total air chlorothalonil concentration from the three spray trials (r (2) = 0.000, P = 0.907 for TL; r (2) = 0.001, P = 0.874 for percent DNA). In addition, no significant difference in DNA damage was observed between exposed (at 0 m) and control animals (P = 0.357 for TL; P = 0.958 for percent DNA). Based on these results it can be concluded that wild small mammals living beside fields sprayed with chlorothalonil are at no greater risk of exposure-related DNA damage than conspecifics from unexposed areas.