Dear Friends,
This is my 3rd presentation, which will help you to understand the depth knowledge of acute eye irritation/corrosion (OECD-405) study in rabbit.
Dermal Irritation and Dermal Toxicity Studies Dinesh Gangoda
Dermal irritation and Corrosion test guidelines 204.
Dermal irritation is the production of reversible damage of the skin following the application of a test chemical for up to 4 hours.
Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. [1]
Dermal corrosion is the production of irreversible damage of the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test chemical for up to four hours.[2]
REFERENCES
OECD/OCDE, Test No. 404: ‘‘Acute Dermal Irritation/Corrosion’’, 28 July 2015 OECD Publishing, peris, Page no, 1- 8.
Robert A., Turner., Screening Methods in Pharmacology; 1st edition; Academic press an imprint of Elsevier, pp, 279- 281.
OECD Guideline for testing of chemicals (1981). ‘‘Repeated Dose Dermal Toxicity’’, 21/28- day Study.
This presentation will help understanding the vast process of rat and mice handling and oral routes of drug administration through acute class method (OECD: 423).
Regulatory guidelines for conducting toxicity studies by ichAnimatedWorld
ICH is the “International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for
Human Use”
ICH is a joint initiative involving both regulators and research based industry representatives of the EU, Japan and the US in
scientific and technical discussions of the testing procedures required
to assess and ensure the safety, quality and efficacy of medicines
Dermal Irritation and Dermal Toxicity Studies Dinesh Gangoda
Dermal irritation and Corrosion test guidelines 204.
Dermal irritation is the production of reversible damage of the skin following the application of a test chemical for up to 4 hours.
Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. [1]
Dermal corrosion is the production of irreversible damage of the skin; namely, visible necrosis through the epidermis and into the dermis, following the application of a test chemical for up to four hours.[2]
REFERENCES
OECD/OCDE, Test No. 404: ‘‘Acute Dermal Irritation/Corrosion’’, 28 July 2015 OECD Publishing, peris, Page no, 1- 8.
Robert A., Turner., Screening Methods in Pharmacology; 1st edition; Academic press an imprint of Elsevier, pp, 279- 281.
OECD Guideline for testing of chemicals (1981). ‘‘Repeated Dose Dermal Toxicity’’, 21/28- day Study.
This presentation will help understanding the vast process of rat and mice handling and oral routes of drug administration through acute class method (OECD: 423).
Regulatory guidelines for conducting toxicity studies by ichAnimatedWorld
ICH is the “International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for
Human Use”
ICH is a joint initiative involving both regulators and research based industry representatives of the EU, Japan and the US in
scientific and technical discussions of the testing procedures required
to assess and ensure the safety, quality and efficacy of medicines
Alternative methods to animals testing are the development and implementation of test method that avoid use of live animals or use of less animals in method.
The council directive on protection of animals used for experiments and scientific purpose in article 23
“The commission and member states should encourage
research into development and validation of alternative methods which could provide the same level of information as that obtained in experiment using animals but which involves less animal”.
Alternative methods able to do:
Reduce Refine Replace
collectively called as “The 3Rs Principle”.
Needs for alternative methods
Because in laboratory animals may be:
Poisoned.
Deprived of food water and sleep.
Applied with skin and eye irritants.
Subjected to psychological stress.
Deliberately infected with the infected disease.
OECD Test Guideline 420: Acute Oral Toxicity - Fixed Dosepp_shivgunde
OECD Test Guideline 420: Acute Oral Toxicity - Fixed Dose
Guideline 420 was adopted in July 1992 as the first alternative to the conventional acute toxicity test.
toxicology study according to OECD guidelines, organisation for economic co-orporation and developement, jasdeep singh , maharaja ranjit singh punjab technical university bathinda
Acute eye irritation test as per OECD guidelinesmadhvi Chaubey
toxicological testing studies as per OECD guidline.
Toxicology is the branch of biology, chemistry and medicine concerned with the study of the adverse effects of chemicals on living organisms.
As per OECD test no. 405 : acute eye irritation test should be done as according to the procedure mentioned under guideline's section.
In this slide contains diabetics, classification, symptoms, complication, invivo and invitro screening models of anti diabetics.
Presented by: GEETHANJALI ADAPALA (Department of pharmacology).
RIPER, anantapur
genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic substances are mutagenic
Alternative methods to animals testing are the development and implementation of test method that avoid use of live animals or use of less animals in method.
The council directive on protection of animals used for experiments and scientific purpose in article 23
“The commission and member states should encourage
research into development and validation of alternative methods which could provide the same level of information as that obtained in experiment using animals but which involves less animal”.
Alternative methods able to do:
Reduce Refine Replace
collectively called as “The 3Rs Principle”.
Needs for alternative methods
Because in laboratory animals may be:
Poisoned.
Deprived of food water and sleep.
Applied with skin and eye irritants.
Subjected to psychological stress.
Deliberately infected with the infected disease.
OECD Test Guideline 420: Acute Oral Toxicity - Fixed Dosepp_shivgunde
OECD Test Guideline 420: Acute Oral Toxicity - Fixed Dose
Guideline 420 was adopted in July 1992 as the first alternative to the conventional acute toxicity test.
toxicology study according to OECD guidelines, organisation for economic co-orporation and developement, jasdeep singh , maharaja ranjit singh punjab technical university bathinda
Acute eye irritation test as per OECD guidelinesmadhvi Chaubey
toxicological testing studies as per OECD guidline.
Toxicology is the branch of biology, chemistry and medicine concerned with the study of the adverse effects of chemicals on living organisms.
As per OECD test no. 405 : acute eye irritation test should be done as according to the procedure mentioned under guideline's section.
In this slide contains diabetics, classification, symptoms, complication, invivo and invitro screening models of anti diabetics.
Presented by: GEETHANJALI ADAPALA (Department of pharmacology).
RIPER, anantapur
genotoxicity describes the property of chemical agents that damages the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, whereas not all genotoxic substances are mutagenic
the presentation is based on OECD guideline of chemical test on acute eye irritation guideline 403, it also give knowledge about why the guideline was updated and analgesic and anesthetic uses on the albino rabbit eye so to overcome the animal distress, and pain. the presentation explain the full guideline in detail
Toxicity is the science dealing with properties, action, toxicity, fatal dose detection or interpretation of result of toxicological analysis & treatment of poison.
Toxicity studies helps to avoid adverse effect and enhance the safety of drug.
This slide provides the information about toxicity screening on experimental animals.
Skin sensitisation, OECD Test guideline 406 .pptxNikitaBankoti2
Skin Sensitisation: ( allergic contact dermatitis) is an immunologically mediated cutaneous reaction to a substance. In the human, the responses may be characterised by pruritis, erythema, oedema, papules, vesicles or a combination of these. In other species the reactions may differ and only erythema and oedema may be seen.
This presentation provides an in-depth examination of dermal irritation and corrosion, focusing on the principles, testing methods, and safety measures involved. Participants will gain insight into the mechanisms underlying dermal irritation and corrosion, as well as the potential risks posed by various substances. Through a detailed exploration of testing protocols such as the Draize test and in vitro alternatives, attendees will learn how these assessments are conducted to ensure product safety and regulatory compliance. Join us to deepen your understanding of dermal irritation and corrosion, essential for ensuring the safety and well-being of consumers and workers alike.
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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2. OECD Guidelines for Testing of Chemicals are periodically reviewed to ensure that
they reflect the best available science.
The latest update mainly focused on the use of analgesics and anesthetics without
impacting the basic concept and structure of the Test Guideline.
ICCVAM and an independent international scientific peer review panel reviewed
the usefulness and limitations of routinely using topical anesthetics, systemic
analgesics, and humane endpoints during in vivo ocular irritation safety testing.
The review concluded that the use of topical anesthetics and systemic analgesics
could avoid most or all pain and distress without affecting the outcome of the test,
and recommended that these substances should always be used.
Topical anesthetics, systemic analgesics, and humane endpoints should be
routinely used during acute eye irritation and corrosion in vivo testing.
Exceptions to their use should be justified. The refinements described in this
proposal will substantially reduce or avoid animal pain and distress in most testing
situations where in vivo ocular safety testing is still necessary.
3. BALANCED PREEMPTIVE PAIN MANAGEMENT SHOULD
INCLUDE:
Routine pretreatment with a topical anesthetic (e.g., proparacaine or tetracaine)
and a systemic analgesic (e.g. buprenorphine).
Routine post-treatment schedule of systemic analgesia (e.g., buprenorphine and
meloxicam).
Scheduled observation, monitoring, and recording of animals for clinical signs of
pain and/or distress, and
Scheduled observation, monitoring, and recording of the nature, severity, and
progression of all eye injuries.
No additional topical anesthetics or analgesics should be applied in order to avoid
interference with the study.
Analgesics with anti-inflammatory activity (e.g., meloxicam) should not be applied
topically, and doses used systemically should not interfere with ocular effects.
4. PRINCIPLE OF THE IN VIVO TEST
Following pretreatment with a systemic analgesic and induction of appropriate
topical anesthesia, the substance to be tested is applied in a single dose to one of
the eyes of the experimental animal; the untreated eye serves as the control.
The degree of eye irritation/corrosion is evaluated by scoring lesions of
conjunctiva, cornea, and iris, at specific intervals.
Other effects in the eye and adverse systemic effects are also described to provide a
complete evaluation of the effects.
The duration of the study should be sufficient to evaluate the reversibility or
irreversibility of the effects.
Animals showing signs of severe distress and/or pain at any stage of the test or
lesions consistent with the humane endpoints described in this Test Guideline
should be humanely killed, and the substance assessed accordingly.
Criteria for making the decision to humanely kill moribund and severely suffering
animals are the subject of a separate Guidance Document.
5. PREPARATIONS FOR THE IN VIVO TEST
Selection of species
The albino rabbit is the preferable laboratory animal and healthy young adult
animals are used. A rationale for using other strains or species should be provided.
Preparation of animals
Both eyes of each experimental animal provisionally selected for testing should be
examined within 24 hours before testing starts.
Animals showing eye irritation, ocular defects, or pre-existing corneal injury
should not be used.
Housing and feeding conditions
Animals should be individually housed.
The temperature should be 20°C (± 3°C) for rabbits.
Relative humidity should be at least 30% and preferably not exceed 70%, other
than during room cleaning; the aim should be 50-60%.
Lighting should be 12 hours light, 12 hours dark.
6. TEST PROCEDURE
Use of topical anesthetics and systemic analgesics
The following procedures are recommended to avoid or minimize pain and
distress in ocular safety testing procedures.
Sixty minutes prior to test substance application (TSA), buprenorphine 0.01
mg/kg is administered by subcutaneous injection (SC) to provide a therapeutic
level of systemic analgesia.
Five minutes prior to TSA, one or two drops of a topical ocular anesthetic (e.g.
0.5% proparacaine hydrochloride or 0.5% tetracaine hydrochloride) are
applied to each eye.
The eye of each animal that is not treated with a test article, but which is
treated with topical anesthetics, serves as a control.
Eight hours after TSA, buprenorphine 0.01 mg/kg SC and meloxicam 0.5
mg/kg SC are administered to provide a continued therapeutic level of
systemic analgesia.
After the initial 8-hour post-TSA treatment, buprenorphine 0.01 mg/kg SC
should be administered every 12 hours, in conjunction with meloxicam 0.5
mg/kg SC every 24 hours, until the ocular lesions resolve and no clinical signs
of pain and distress are present.
7. “Rescue” analgesia should be given immediately after TSA if pre-emptive
analgesia and topical anesthesia are inadequate. If an animal shows signs of
pain and distress during the study, a “rescue” dose of buprenorphine 0.03
mg/kg SC would be given immediately and repeated as often as every 8
hours, if necessary, instead of 0.01 mg/kg SC every 12 hours. Meloxicam 0.5
mg/kg SC would be administered every 24 hours in conjunction with the
“rescue” dose of buprenorphine, but not until at least 8 hours post-TSA.
Application of the test substance
The test substance should be placed in the conjunctival sac of one eye of each
animal after gently pulling the lower lid away from the eyeball.
The lids are then gently held together for about one second in order to
prevent loss of the material.
The other eye, which remains untreated, serves as a control.
Irrigation
The eyes of the test animals should not be washed for at least 24 hours
following instillation of the test substance, except for solids and in case of
immediate corrosive or irritating effects.
At 24 hours a washout may be used if considered appropriate.
8. DOSE LEVEL
(1) Testing of liquids
For testing liquids, a dose of 0.1 mL is used.
Pump sprays should not be used for instilling the substance directly into the
eye.
The liquid spray should be expelled and collected in a container prior to
instilling 0.1 mL into the eye.
(2) Testing of solids
When testing solids, pastes, and particulate substances, the amount used
should have a volume of 0.1 mL or a weight of not more than 100 mg.
The test material should be ground to a fine dust.
The volume of solid material should be measured after gently compacting it,
e.g. by tapping the measuring container.
If the solid test substance has not been removed from the eye of the test
animal by physiological mechanisms at the first observation time point of 1
hour after treatment, the eye may be rinsed with saline or distilled water.
9. (3) Testing of aerosols
It is recommended that all pump sprays and aerosols be collected prior to
instillation into the eye.
The one exception is for substances in pressurised aerosol containers, which
cannot be collected due to vaporisation. In such cases, the eye should be held
open, and the test substance administered to the eye in a simple burst of about one
second, from a distance of 10 cm directly in front of the eye.
This distance may vary depending on the pressure of the spray and its contents.
Care should be taken not to damage the eye from the pressure of the spray.
In appropriate cases, there may be a need to evaluate the potential for
“mechanical” damage to the eye from the force of the spray.
initial test (in vivo eye irritation/corrosion):
Initially using one animal.
Observations should allow for determination of severity and reversibility
before proceeding to a confirmatory test in a second animal.
If the results of this test indicate the substance to be corrosive or a severe
irritant to the eye using the procedure described, further testing for ocular
irritancy should not be performed.
10. Confirmatory test (in vivo eye irritation test):
If a corrosive or severe irritant effect is not observed in the initial test, the irritant
or negative response should be confirmed using up to two additional animals.
If an irritant effect is observed in the initial test, it is recommended that the
confirmatory test be conducted in a sequential manner in one animal at a time,
rather than exposing the two additional animals simultaneously.
If the second animal reveals corrosive or severe irritant effects, the test is not
continued.
If results from the second animal are sufficient to allow for a hazard classification
determination, then no further testing should be conducted.
Observation period
The duration of the observation period should be sufficient to evaluate fully
the magnitude and reversibility of the effects observed.
The experiment should be terminated at any time that the animal shows signs
of severe pain or distress.
To determine reversibility of effects, the animals should be observed normally
for 21 days post administration of the test substance.
If reversibility is seen before 21 days, the experiment should be terminated at
that time.
11. Clinical observations and grading of eye reactions :
The eyes should be comprehensively evaluated for the presence or
absence of ocular lesions one hour post-TSA, followed by at least daily
evaluations.
Animals should be evaluated several times daily for the first 3 days to
ensure that termination decisions are made in a timely manner.
Test animals should be routinely evaluated for the entire duration of the
study for clinical signs of pain and/or distress (e.g. repeated pawing or
rubbing of the eye, excessive blinking, excessive tearing) at least twice
daily, with a minimum of 6 hours between observations, or more often
if necessary.
Fluorescein staining should be routinely used and a slit lamp
biomicroscope used when considered appropriate (e.g., assessing depth
of injury when corneal ulceration is present) as an aid in the detection
and measurement of ocular damage, and to evaluate if established
endpoint criteria for humane euthanasia have been met.
12. Digital photographs of observed lesions may be collected for reference and to
provide a permanent record of the extent of ocular damage.
Animals showing severe pain or distress should be humanely killed without
delay, and the substance assessed accordingly.
Animals with the following eye lesions post-instillation
should be humanely killed:
a. corneal perforation or significant corneal ulceration including staphyloma;
b. blood in the anterior chamber of the eye.
c. grade 4 corneal opacity.
d. absence of a light reflex (iridial response grade 2) which persists for 72
hours;
e. ulceration of the conjunctival membrane;
f. necrosis of the conjunctivae or nictitating membrane; or sloughing.
g. This is because such lesions generally are not reversible. Furthermore, it is
recommended that the following ocular lesions be used as humane
endpoints to terminate studies before the end of the scheduled 21-day
observation period
13. The grades of ocular reaction (conjunctivae, cornea and iris) should be
obtained and recorded at 1, 24, 48, and 72 hours following test substance
application (Table 1).
Animals that do not develop ocular lesions may be terminated not earlier than
3 days post instillation.
Animals with ocular lesions that are not severe should be observed until the
lesions clear, or for 21 days, at which time the study is terminated.
Observations should be performed and recorded at a minimum of 1 hour, 24
hours, 48 hours, 72 hours, 7 days, 14 days, and 21 days in order to determine the
status of the lesions, and their reversibility or irreversibility.
Examination of reactions can be facilitated by use of a binocular loupe, hand
slit-lamp, biomicroscope, or other suitable device.
After recording the observations at 24 hours, the eyes may be further examined
with the aid of fluorescein.