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The critical feature of many xenobiotics is the drug gradient from the concentrated tear reservoir to the relatively barren corneal and conjunctival epithelia, which forces a passive route of absorption. The same is true in the opposite direction, towards the ocular surface (OS). With the premise that tears can be regarded as equivalent to or a substitute for plasma, researchers may determine drug concentrations in the OS fluid. Within this framework, a survey of scholarly sources on the topic was conducted. It provided an overview of current knowledge, allowing the identification of relevant theories, methods, and gaps in the existing research that can be employed in subsequent research. OS fluid (tears particularly) has enormous potential as a source of biological material for external drug screening and as a biomarker of various systemic diseases. Given the numerous alternate matrices, knowledge of their properties is very important in selecting the most appropriate specimens in toxicological analyses.<\/jats:p>","DOI":"10.3390\/toxics12070513","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T15:05:51Z","timestamp":1721142351000},"page":"513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ocular Surface Fluid: More than a Matrix"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6869-3734","authenticated-orcid":false,"given":"Ivan","family":"\u0160o\u0161a","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Levine, B.S., and Kerrigan, S. (2020). Human Performance Toxicology. Principles of Forensic Toxicology, Springer International Publishing.","DOI":"10.1007\/978-3-030-42917-1"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Levine, B.S., and Kerrigan, S. (2020). Postmortem Forensic Toxicology. Principles of Forensic Toxicology, Springer International Publishing.","DOI":"10.1007\/978-3-030-42917-1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11419-021-00596-5","article-title":"Alternative matrices in forensic toxicology: A critical review","volume":"40","author":"Monedeiro","year":"2022","journal-title":"Forensic Toxicol."},{"key":"ref_4","unstructured":"Louzao, M.C., and Costas, C. (2024). 4.1. 1 The Three Rs. Environmental Toxicology: Non-Bacterial Toxins, Walter de Gruyter."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1111\/j.1442-9071.2012.02758.x","article-title":"Fluids of the ocular surface: Concepts, functions and physics","volume":"40","author":"Cher","year":"2012","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109101","DOI":"10.1016\/j.exer.2022.109101","article-title":"Biochemistry of human tear film: A review","volume":"220","author":"Masoudi","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"339","DOI":"10.5935\/0034-7280.20150071","article-title":"Drop volume of artificial tear solutions: Pharmacoeconomic study","volume":"74","author":"Costa","year":"2015","journal-title":"Rev. Bras. Oftalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/IIO.0000000000000162","article-title":"Tear Volume-based Diagnostic Classification for Tear Dysfunction","volume":"57","author":"Pflugfelder","year":"2017","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Schaudig, U., Shams, P., and Ducasse, A. (2024). Anatomy and Physiology of the Lacrimal System. Oculoplastic, Lacrimal and Orbital Surgery: The ESOPRS Textbook: Volume 1, Springer.","DOI":"10.1007\/978-3-031-39634-2_37"},{"key":"ref_10","unstructured":"Price, K.M., and Richard, M.J. (2009). The tearing patient: Diagnosis and management. Am. Acad. Ophthalmol., 33\u201335."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1208\/s12249-023-02516-9","article-title":"Ocular Drug Delivery: A Comprehensive Review","volume":"24","author":"Ahmed","year":"2023","journal-title":"AAPS PharmSciTech"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tai, J., Han, M., Lee, D., Park, I.H., Lee, S.H., and Kim, T.H. (2022). Different Methods and Formulations of Drugs and Vaccines for Nasal Administration. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14051073"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Le, T., Aguilar, B., Mangal, J.L., and Acharya, A.P. (2022). Oral drug delivery for immunoengineering. Bioeng. Transl. Med., 7.","DOI":"10.1002\/btm2.10243"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Caselli, E., Soffritti, I., Lamberti, G., D\u2019Accolti, M., Franco, F., Demaria, D., Contoli, M., Passaro, A., Contini, C., and Perri, P. (2020). Anti-SARS-CoV-2 IgA Response in Tears of COVID-19 Patients. Biology, 9.","DOI":"10.3390\/biology9110374"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/jcp.21589","article-title":"Conjunctival sac fluid contains elevated levels of soluble TRAIL: Implications for the anti-tumoral surveillance of the anterior surface of the eye","volume":"218","author":"Secchiero","year":"2009","journal-title":"J. Cell. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"109913","DOI":"10.1016\/j.exer.2024.109913","article-title":"Raman spectroscopy assisted tear analysis: A label free, optical approach for noninvasive disease diagnostics","volume":"243","author":"Thomas","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_17","first-page":"2748","article-title":"Human microbiome of eyelid skin, conjunctival sac, and meibum of the meibomian gland","volume":"60","author":"Suzuki","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Amini, P., and Okeme, J. (2023). Tear Fluid as a Matrix for Biomonitoring Environmental and Chemical Exposures. Curr. Environ. Health Rep., 1\u201316.","DOI":"10.21203\/rs.3.rs-3711147\/v2"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1016\/j.jprot.2012.04.053","article-title":"In-depth analysis of the human tear proteome","volume":"75","author":"Zhou","year":"2012","journal-title":"J. Proteom."},{"key":"ref_20","unstructured":"Chang, A.Y., and Purt, B. (2021). Biochemistry, Tear Film, StatPearls Publishing."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.survophthal.2003.12.009","article-title":"Determinants of eye drop size","volume":"49","author":"Ludwig","year":"2004","journal-title":"Surv. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1038\/s41433-020-0930-0","article-title":"Tear analysis as the next routine body fluid test","volume":"34","author":"Barmada","year":"2020","journal-title":"Eye"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10064","DOI":"10.1038\/s41598-021-89514-8","article-title":"Diagnostic biomarkers in tear fluid: From sampling to preanalytical processing","volume":"11","author":"Bachhuber","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6207","DOI":"10.1021\/acs.analchem.9b05078","article-title":"Schirmer Paper Noninvasive Microsampling for Direct Mass Spectrometry Analysis of Human Tears","volume":"92","author":"Yao","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Milevoj Kopcinovic, L., Culej, J., Jokic, A., Bozovic, M., and Kocijan, I. (2020). Laboratory testing of extravascular body fluids: National recommendations on behalf of the Croatian Society of Medical Biochemistry and Laboratory Medicine. Part I\u2014Serous fluids. Biochem. Med., 30.","DOI":"10.11613\/BM.2020.010502"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nioi, M., Napoli, P.E., Demontis, R., Locci, E., Fossarello, M., and d\u2019Aloja, E. (2021). Postmortem Ocular Findings in the Optical Coherence Tomography Era: A Proof of Concept Study Based on Six Forensic Cases. Diagnostics, 11.","DOI":"10.3390\/diagnostics11030413"},{"key":"ref_27","unstructured":"Peter, C., and Kamil Hakan, D. (2024). Postmortem Interval Ocular Indicators. Contemporary Issues in Clinical Bioethics\u2014Medical, Ethical and Legal Perspectives, IntechOpen."},{"key":"ref_28","first-page":"20150382","article-title":"Quantitative mass spectrometry: An overview","volume":"374","author":"Urban","year":"2016","journal-title":"Philos. Trans. A Math. Phys. Eng. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1039\/D3AY01583A","article-title":"Trace analysis of steroid hormones in tear films via liquid chromatography-high resolution mass spectrometry","volume":"16","author":"Huang","year":"2024","journal-title":"Anal. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110","DOI":"10.5935\/0004-2749.20150028","article-title":"Impact of wildfire smoke in Buenos Aires, Argentina, on ocular surface","volume":"78","author":"Berra","year":"2015","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"481","DOI":"10.5935\/0004-2749.20180091","article-title":"Impact of environmental pollution on the ocular surface of Sjogren\u2019s syndrome patients","volume":"81","author":"Galperin","year":"2018","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.cyto.2008.05.011","article-title":"Tear cytokine and ocular surface alterations following brief passive cigarette smoke exposure","volume":"43","author":"Rummenie","year":"2008","journal-title":"Cytokine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.ophtha.2011.11.015","article-title":"Oral alcohol administration disturbs tear film and ocular surface","volume":"119","author":"Kim","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6948","DOI":"10.1007\/s11356-019-04134-0","article-title":"Comparative study of tear lipid composition in two human populations with different exposure to particulate matter in La Plata, Argentina","volume":"26","author":"Gutierrez","year":"2019","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18052","DOI":"10.1038\/s41598-022-22550-0","article-title":"Clinical association between trace elements of tear and dry eye metrics","volume":"12","author":"Chen","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1080\/09273940802283323","article-title":"Complement activation in tear fluid during occupational mold challenge","volume":"16","author":"Peltonen","year":"2008","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Matsuda, M., Bonatti, R., Marquezini, M.V., Garcia, M.L., Santos, U.P., Braga, A.L., Alves, M.R., Saldiva, P.H., and Monteiro, M.L. (2015). Lacrimal Cytokines Assessment in Subjects Exposed to Different Levels of Ambient Air Pollution in a Large Metropolitan Area. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143131"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"18359","DOI":"10.1038\/s41598-022-23294-7","article-title":"Evidence of air pollution-related ocular signs and altered inflammatory cytokine profile of the ocular surface in Beijing","volume":"12","author":"Jing","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8054","DOI":"10.1167\/iovs.15-18398","article-title":"The Effect of Ambient Ozone on Unsaturated Tear Film Wax Esters","volume":"56","author":"Paananen","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Girshevitz, O., Cohen-Sinai, N., Zahavi, A., Vardizer, Y., Fixler, D., and Goldenberg-Cohen, N. (2022). Trace Elements in Tears: Comparison of Rural and Urban Populations Using Particle Induced X-ray Emission. J. Pers. Med., 12.","DOI":"10.3390\/jpm12101633"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1097\/ICO.0000000000001173","article-title":"Application of Scanning Electron Microscopy with Energy-Dispersive X-Ray Spectroscopy for Analyzing Ocular Surface Particles on Schirmer Strips","volume":"36","author":"Avula","year":"2017","journal-title":"Cornea"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1097\/ICO.0000000000002087","article-title":"Human Ocular Surface Particulate Composition in the Clinical Versus Home Environment","volume":"38","author":"Kaplan","year":"2019","journal-title":"Cornea"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1177\/1120672121998922","article-title":"Tear fluid collection methods: Review of current techniques","volume":"31","author":"Pieczynski","year":"2021","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_44","first-page":"e50972","article-title":"Tear Samples for Protein Extraction: Comparative Analysis of Schirmer\u2019s Test Strip and Microcapillary Tube Methods","volume":"15","author":"Tham","year":"2023","journal-title":"Cureus"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109083","DOI":"10.1016\/j.exer.2022.109083","article-title":"Viscoelastic properties of the human tear film","volume":"219","author":"Recchioni","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"del Amo, E.M. (2022). Topical ophthalmic administration: Can a drug instilled onto the ocular surface exert an effect at the back of the eye?. Front. Drug Deliv., 2.","DOI":"10.3389\/fddev.2022.954771"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3109\/02713688509025164","article-title":"Secretion of drugs in tears","volume":"4","year":"1985","journal-title":"Curr. Eye Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/jac\/dkl224","article-title":"Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines","volume":"58","author":"Agwuh","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1111\/vop.12783","article-title":"Tear film concentrations of topically applied 0.5% oxytetracycline ointment in normal canine eyes","volume":"23","author":"Sigmund","year":"2020","journal-title":"Vet. Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ejpb.2016.11.034","article-title":"Food, gastrointestinal pH, and models of oral drug absorption","volume":"112","author":"Abuhelwa","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1080\/17425255.2021.1951223","article-title":"Crosstalk of physiological pH and chemical pKa under the umbrella of physiologically based pharmacokinetic modeling of drug absorption, distribution, metabolism, excretion, and toxicity","volume":"17","author":"Gaohua","year":"2021","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S1542-0124(12)70233-1","article-title":"The tear film and the optical quality of the eye","volume":"8","author":"Cervino","year":"2010","journal-title":"Ocul. Surf."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3928\/1081597X-20220713-02","article-title":"Fresh Human Myopic Lenticule Intrastromal Implantation for Keratoconus Using SMILE Surgery in a Long-term Follow-up Study: Ultrastructural Analysis by Transmission Electron Microscopy","volume":"38","author":"Semiz","year":"2022","journal-title":"J. Refract. Surg."},{"key":"ref_54","unstructured":"Shumway, C.L., Motlagh, M., and Wade, M. (2024). Anatomy, Head and Neck, Eye Conjunctiva. StatPearls, StatPearls Publishing."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Santana, C.P., Matter, B.A., Patil, M.A., Silva-Cunha, A., and Kompella, U.B. (2023). Corneal Permeability and Uptake of Twenty-Five Drugs: Species Comparison and Quantitative Structure-Permeability Relationships. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061646"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1208\/s12249-021-01977-0","article-title":"Review of Approaches for Increasing Ophthalmic Bioavailability for Eye Drop Formulations","volume":"22","author":"Lanier","year":"2021","journal-title":"AAPS PharmSciTech"},{"key":"ref_57","first-page":"193","article-title":"Unlocking the Potential of Eyelid Skin-Based Drug Delivery: A Filipino Pharmaceutical Scientist\u2019s Journey","volume":"80","author":"See","year":"2020","journal-title":"J. Pharm. Sci. Technol. Jpn."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Derakhshani, A., Hasani, S., and Navaei, T. (2023). Hemocompatible polymers for medical applications. Handbook of Polymers in Medicine, Elsevier.","DOI":"10.1016\/B978-0-12-823797-7.00005-8"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"105553","DOI":"10.1016\/j.ejps.2020.105553","article-title":"Topical ocular pharmacokinetics and bioavailability for a cocktail of atenolol, timolol and betaxolol in rabbits","volume":"155","author":"Fayyaz","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s13346-016-0339-2","article-title":"A comprehensive insight on ocular pharmacokinetics","volume":"6","author":"Agrahari","year":"2016","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4103\/ijo.IJO_646_17","article-title":"Anatomy of cornea and ocular surface","volume":"66","author":"Sridhar","year":"2018","journal-title":"Indian J. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"120924","DOI":"10.1016\/j.ijpharm.2021.120924","article-title":"Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies","volume":"607","author":"Mofidfar","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1039\/D3NH00306J","article-title":"Enhancing paracellular and transcellular permeability using nanotechnological approaches for the treatment of brain and retinal diseases","volume":"9","author":"Khalil","year":"2024","journal-title":"Nanoscale Horiz."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"336","DOI":"10.3390\/futurepharmacol4020019","article-title":"Ocular Drug Delivery into the Eyes Using Drug-Releasing Soft Contact Lens","volume":"4","author":"Tashima","year":"2024","journal-title":"Future Pharmacol."},{"key":"ref_65","unstructured":"Bartlett, J.D., and Jaanus, S.D. (2007). Clinical Ocular Pharmacology, Elsevier Health Sciences."},{"key":"ref_66","first-page":"165","article-title":"Discussion on the Development of New Ophthalmic Dosage Forms of Ganciclovir and Its Pre-Development Evaluation","volume":"2021","author":"Zhang","year":"2021","journal-title":"CONVERTER"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ejps.2018.03.034","article-title":"Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye","volume":"119","author":"Ramsay","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3109\/10717544.2014.943336","article-title":"Liposomes in topical ophthalmic drug delivery: An update","volume":"23","author":"Agarwal","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3121\/cmr.2019.1486","article-title":"Neuropsychiatric Adverse Events from Topical Ophthalmic Timolol","volume":"17","author":"Cimolai","year":"2019","journal-title":"Clin. Med. Res."},{"key":"ref_70","unstructured":"Reed, S.M., Bayly, W.M., and Sellon, D.C. (2018). Disorders of the Eye and Vision. Equine Internal Medicine, W.B. Saunders."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1007\/s00405-022-07290-1","article-title":"Distribution of cocaine-induced midline destructive lesions: Systematic review and classification","volume":"279","author":"Nitro","year":"2022","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_72","unstructured":"(2018). Methods in Toxicology. Toxicology and Risk Assessment, Wiley."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4309","DOI":"10.1080\/21655979.2022.2031412","article-title":"Active pharmaceutical ingredient (API) chemicals: A critical review of current biotechnological approaches","volume":"13","author":"Kumar","year":"2022","journal-title":"Bioengineered"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.ijpharm.2017.09.018","article-title":"Physicochemical properties of mucus and their impact on transmucosal drug delivery","volume":"532","author":"Leal","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3385","DOI":"10.1007\/s10792-023-02746-7","article-title":"Topographic and anatomical features of the nasolacrimal duct obstruction due to radioiodine treatment","volume":"43","author":"Yartsev","year":"2023","journal-title":"Int. Ophthalmol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"403","DOI":"10.18203\/issn.2454-5929.ijohns20210182","article-title":"Anatomy of the lacrimal apparatus from a rhinologist\u2019s perspective: A review","volume":"7","author":"Munjal","year":"2021","journal-title":"Int. J. Otorhinolaryngol. Head Neck Surg."},{"key":"ref_77","unstructured":"Law, S.K., and Lee, D.A. (2020). Ocular pharmacology. Glaucoma Medical Therapy-Principles and Management, Kugler Publications."},{"key":"ref_78","unstructured":"Morton, S., Crucian, B., Hagan, S., Satyamitra, M., and Daily, A. (2018, January 22\u201325). Pilot study on the investigation of tear fluid biomarkers as an indicator of ocular, neurological, and immunological health in astronauts. Proceedings of the NASA Human Research Program Investigators\u2019 Workshop (HRP IWS 2018), Galveston, TX, USA."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Tomeckova, V., Tkacikova, S., Talian, I., Fabriciova, G., Hovan, A., Kondrakhova, D., Zakutanska, K., Skirkova, M., Komanicky, V., and Tomasovicova, N. (2023). Experimental Analysis of Tear Fluid and Its Processing for the Diagnosis of Multiple Sclerosis. Sensors, 23.","DOI":"10.3390\/s23115251"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1002\/pds.1466","article-title":"An instructive example of a long-latency adverse drug reaction\u2014Sclerosing peritonitis due to practolol","volume":"16","author":"Mann","year":"2007","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/vop.12991","article-title":"A prospective, masked, randomized, controlled superiority study comparing the incidence of corneal injury following general anesthesia in dogs with two methods of corneal protection","volume":"25","author":"Ioannides","year":"2022","journal-title":"Vet. Ophthalmol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.hgmx.2016.10.007","article-title":"Advantages of ketamine as a perioperative analgesic","volume":"81","year":"2018","journal-title":"Rev. M\u00e9dica Del Hosp. Gen. De M\u00e9xico"},{"key":"ref_83","unstructured":"Suresh, A.B., Rosani, A., Patel, P., and Wadhwa, R. (2023). Rifampin. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_84","unstructured":"Hasson, H. (2024, July 14). Generalized Onset Tonic-Clonic Seizures. MedLink. Available online: https:\/\/www.medlink.com\/articles\/generalized-onset-tonic-clonic-seizures."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.genhosppsych.2013.04.013","article-title":"Drops of madness? Recreational misuse of tropicamide collyrium; early warning alerts from Russia and Italy","volume":"35","author":"Bersani","year":"2013","journal-title":"Gen. Hosp. Psychiatry"},{"key":"ref_86","first-page":"522","article-title":"Abuse of tropicamide eye drops: Review of clinical data","volume":"44","author":"Bellman","year":"2022","journal-title":"Braz. J. Psychiatry"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.forsciint.2012.01.001","article-title":"Detection of drugs of abuse in simultaneously collected oral fluid, urine and blood from Norwegian drug drivers","volume":"219","author":"Vindenes","year":"2012","journal-title":"Forensic Sci. Int."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Roque Bravo, R., Faria, A.C., Brito-da-Costa, A.M., Carmo, H., Mladenka, P., Dias da Silva, D., Remiao, F., and On Behalf of The Oemonom, R. (2022). Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern. Toxins, 14.","DOI":"10.3390\/toxins14040278"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Dualde, P., Miralles, P., Peris-Martinez, C., Yusa, V., and Coscolla, C. (2023). Untargeted analysis and tentative identification of unknown substances in human tears by ultra-high performance liquid chromatography-high resolution mass spectrometry: Pilot study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 1228.","DOI":"10.1016\/j.jchromb.2023.123832"}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/7\/513\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:17:42Z","timestamp":1760109462000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/12\/7\/513"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,16]]},"references-count":89,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["toxics12070513"],"URL":"https:\/\/doi.org\/10.3390\/toxics12070513","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,16]]}}}