This document provides information on acute eye irritation testing methods. It discusses using topical anesthetics and systemic analgesics to minimize animal pain and distress during testing. Procedures are outlined for applying the test substance to a rabbit's eye while maintaining anesthesia. Lesions are then scored at intervals to evaluate irritation effects. The test aims to assess reversibility of eye damage in a humane manner.
The document discusses the Investigational New Drug (IND) application process with the FDA. An IND application allows a company to ship an experimental drug across state lines and begin clinical trials. It must include preclinical data to show the drug is safe for initial human use as well as protocols for proposed studies. The FDA reviews the IND for 30 days before clinical trials may begin to ensure subject safety. The overall goal of an IND is to facilitate testing of new drugs while protecting clinical trial participants.
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.
TEST ITEM CHARACTERIZATION IN REGULATORY TOXICOLOGY STUDIES.pptxashharnomani
This document provides guidance on the characterization of test items used in regulatory toxicology studies according to OECD GLP principles. It defines key terms like test item, batch, vehicle, and formulation. It describes the importance of characterizing test items to confirm their identity and suitability for studies. Guidance is provided on characterizing specific types of test items like those in early development, living organisms, medical devices, and radiolabeled items. The characterization should include information on the test item's source, composition, and relevant properties.
Herg assay,Structure, Various screening methods and AdvantagesUrvashi Shakarwal
The document discusses hERG assays, which are used to screen for compounds that may block the hERG potassium channel and prolong the heart's QT interval, potentially causing fatal arrhythmias. It describes the structure and function of the hERG channel, then summarizes various screening methods for hERG activity including electrophysiology, flux assays, fluorescence-based assays, and radioligand binding assays. These methods allow high-throughput screening of large numbers of compounds early in drug development to improve cardiovascular safety.
This document discusses the requirements for an investigational new drug (IND) application. An IND is required to initiate clinical trials of an unapproved drug and must contain information on animal studies, manufacturing, and clinical trial protocols. The core battery of safety pharmacology studies evaluates effects on major organ systems like the cardiovascular, central nervous, and respiratory systems. These studies are designed to identify potential adverse effects and safety risks before human clinical trials.
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.
The document discusses the Investigational New Drug (IND) application process with the FDA. An IND application allows a company to ship an experimental drug across state lines and begin clinical trials. It must include preclinical data to show the drug is safe for initial human use as well as protocols for proposed studies. The FDA reviews the IND for 30 days before clinical trials may begin to ensure subject safety. The overall goal of an IND is to facilitate testing of new drugs while protecting clinical trial participants.
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.
TEST ITEM CHARACTERIZATION IN REGULATORY TOXICOLOGY STUDIES.pptxashharnomani
This document provides guidance on the characterization of test items used in regulatory toxicology studies according to OECD GLP principles. It defines key terms like test item, batch, vehicle, and formulation. It describes the importance of characterizing test items to confirm their identity and suitability for studies. Guidance is provided on characterizing specific types of test items like those in early development, living organisms, medical devices, and radiolabeled items. The characterization should include information on the test item's source, composition, and relevant properties.
Herg assay,Structure, Various screening methods and AdvantagesUrvashi Shakarwal
The document discusses hERG assays, which are used to screen for compounds that may block the hERG potassium channel and prolong the heart's QT interval, potentially causing fatal arrhythmias. It describes the structure and function of the hERG channel, then summarizes various screening methods for hERG activity including electrophysiology, flux assays, fluorescence-based assays, and radioligand binding assays. These methods allow high-throughput screening of large numbers of compounds early in drug development to improve cardiovascular safety.
This document discusses the requirements for an investigational new drug (IND) application. An IND is required to initiate clinical trials of an unapproved drug and must contain information on animal studies, manufacturing, and clinical trial protocols. The core battery of safety pharmacology studies evaluates effects on major organ systems like the cardiovascular, central nervous, and respiratory systems. These studies are designed to identify potential adverse effects and safety risks before human clinical trials.
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.
The document outlines the studies needed for an Investigational New Drug (IND) submission to the FDA. An IND application must contain information on animal pharmacology and toxicology studies, chemistry and manufacturing, and clinical protocols. It provides a flow chart showing the various preclinical studies required, including chemical and physical properties, biological studies, pharmacology, toxicology, and formulation studies. The goal of the preclinical studies is to generate data for the safety assessment of the new drug in humans.
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.
Regulatory guidelines for conducting toxicity studiesHimikaRathi
This document outlines regulatory guidelines for conducting toxicity studies, focusing on OECD guidelines. It provides an introduction to OECD guidelines and lists numerous guidelines for health effects testing. It defines key terms related to toxicity studies. It describes the objectives and procedures for various types of toxicity studies, including acute toxicity studies conducted over 14 days, subacute studies of 14-28 days, subchronic studies up to 90 days, and chronic studies of 6 months or more. Test guidelines covered include fixed dose, acute toxic class, and up-and-down methods. The document aims to help standardize toxicity testing internationally.
This document outlines the requirements for toxicological studies as specified in Schedule Y of the Drugs and Cosmetics Act of India. It discusses the various medical organizations involved in clinical research regulation and drug development in India. It then describes the key aspects of Schedule Y, including the appendices that cover requirements for non-clinical animal toxicity studies. The appendices specify the types of studies needed, such as single dose toxicity studies, repeated dose toxicity studies, reproductive toxicity studies, and carcinogenicity studies, along with the testing parameters and number of animals required for each.
alternative methods of animal toxicity.pptxashharnomani
Alternative methods to animal toxicity testing are needed because animal testing can cause suffering. Some alternative methods include computer modeling, cell and tissue cultures, and organ chips. Computer modeling uses computer programs to simulate biological effects and predict toxicity without animal testing. Cell and tissue cultures grow isolated cells and tissues in vitro to study toxicity. Organ chips are microfluidic devices that contain living cells arranged to simulate organ-level functions, allowing tests on human-relevant systems without whole animals. These alternative methods can help reduce and replace animal use in toxicity testing.
The document describes the hERG assay, which is used to test for potential drug-induced prolongation of the QT interval. It discusses the hERG gene and potassium channel, how mutations can cause long QT syndrome. It then summarizes three methods for conducting the hERG assay: electrophysiological assay using whole-cell patch clamping, Fluorometric imaging plate reader-based thallium flux assay, and radioligand binding with 35S-MK-499. Details are provided on cell preparation and protocol for each type of hERG assay.
Regulatory guidelines for conducting toxicity studies by ichAnimatedWorld
The document outlines regulatory guidelines for conducting toxicity studies established by the International Council on Harmonization (ICH). ICH provides guidelines on quality, safety, and efficacy for pharmaceutical registration. The safety guidelines cover areas like carcinogenicity studies, genotoxicity testing, toxicokinetics, duration of chronic toxicity testing, reproductive toxicity testing, immunotoxicity studies, phototoxicity evaluation, and nonclinical safety testing to support pediatric medicine development. Expert working groups establish the guidelines to ensure a consistent approach to nonclinical safety assessment is applied across regions.
The document provides an overview of the regulatory process for bringing a new drug to market, beginning with pre-clinical studies and submission of an Investigational New Drug (IND) application to the FDA. If approved, the IND allows clinical trials to be conducted in three phases to evaluate safety and efficacy. If phase 3 trials demonstrate a drug is safe and effective, a New Drug Application or Biologics License Application can be submitted for approval to market the drug. Ongoing monitoring of safety continues even after approval.
REPRODUCTIVE TOXICITY STUDIES, Definition
Introduction, OECD guidelines for reproductive toxicity studies
Principle of the test, Description of Method, Procedure, Experimental Schedule, Data and Reporting, Results, Male Fertility Toxicological Studies
Ms. I. Sai Reddemma.
Department of Pharmacology
Economics of drug discovery. final.pptxashharnomani
The document discusses the economics of drug discovery. It notes that drug discovery is a lengthy and expensive process, taking 3-20 years and costing billions of dollars. Key points include:
- Drug discovery involves identifying potential drug targets and compounds through research. Clinical trials then test compounds on animals and humans.
- Total R&D costs to bring a new drug to market were estimated at $985 million to $1.3 billion in 2020, though some prior estimates were as high as $2.8 billion.
- The majority of costs (40%) go towards clinical trials, with drug discovery and pre-clinical trials accounting for 30-50% of total costs. Failed drug candidates also contribute to overall costs.
The guidelines describe about the subacute toxicity studies in rodents with a comparison with the previous guideline.it also includes the comparison of all three subacute toxicity studies OECD 407, OECD 410, and OECD 412
Screening methods for skin sensitization, skin irritation and dermal toxicity...Ch. Bhargava krishna
This document discusses screening methods for skin sensitization, irritation, and toxicity studies. It describes the Guinea Pig Maximization Test and Buehler Test methods for assessing skin sensitization potential. The Local Lymph Node Assay is presented as a new alternative method that provides more objective data on sensitization potential. For skin irritation screening, the document outlines using rabbits as test subjects and applying a test chemical to the skin to evaluate the degree of irritation.
The document summarizes skin sensitization testing methods according to OECD Guideline 406. It describes two common animal models - the guinea pig and mouse - and tests used, including the Guinea Pig Maximization Test and Buehler Test. It provides details on study design, including number of animals, induction and challenge procedures, observations, and scoring of skin reactions. The goal is to screen substances for their potential to cause skin sensitization or allergic contact dermatitis in humans.
This document discusses safety pharmacology studies, with a focus on respiratory and central nervous system safety pharmacology. It defines safety pharmacology studies as investigating potential undesirable pharmacological effects of substances on physiological functions. For respiratory safety pharmacology, the core battery studies measure respiratory rate, tidal volume, and oxygen saturation. Supplementary studies measure airway resistance and lung compliance. For CNS safety pharmacology, core studies evaluate behavior, locomotor activity, motor coordination, and seizure liability. Safety pharmacology aims to identify risks and inform safe starting doses in clinical trials.
This document summarizes a seminar on safety pharmacology. It defines safety pharmacology and outlines the core battery of studies, which evaluate effects on the central nervous, cardiovascular and respiratory systems. It describes when safety pharmacology studies are needed at different stages of drug development and under various conditions. Guidelines for conducting the studies from organizations like ICH are also discussed.
The document discusses safety pharmacology studies that are conducted to evaluate potential adverse effects of pharmaceutical substances on vital organ systems. It describes the safety pharmacology core battery that investigates effects on the central nervous, cardiovascular and respiratory systems. Follow up studies provide more in-depth understanding of effects on these systems. Supplemental studies evaluate effects on other organ systems like renal, gastrointestinal and immune systems. A variety of evaluation methods are used like functional observation, electrocardiography, plethysmography and biomarkers. Conditions where safety pharmacology studies may not be needed are also outlined.
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
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.
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
The document outlines the studies needed for an Investigational New Drug (IND) submission to the FDA. An IND application must contain information on animal pharmacology and toxicology studies, chemistry and manufacturing, and clinical protocols. It provides a flow chart showing the various preclinical studies required, including chemical and physical properties, biological studies, pharmacology, toxicology, and formulation studies. The goal of the preclinical studies is to generate data for the safety assessment of the new drug in humans.
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.
Regulatory guidelines for conducting toxicity studiesHimikaRathi
This document outlines regulatory guidelines for conducting toxicity studies, focusing on OECD guidelines. It provides an introduction to OECD guidelines and lists numerous guidelines for health effects testing. It defines key terms related to toxicity studies. It describes the objectives and procedures for various types of toxicity studies, including acute toxicity studies conducted over 14 days, subacute studies of 14-28 days, subchronic studies up to 90 days, and chronic studies of 6 months or more. Test guidelines covered include fixed dose, acute toxic class, and up-and-down methods. The document aims to help standardize toxicity testing internationally.
This document outlines the requirements for toxicological studies as specified in Schedule Y of the Drugs and Cosmetics Act of India. It discusses the various medical organizations involved in clinical research regulation and drug development in India. It then describes the key aspects of Schedule Y, including the appendices that cover requirements for non-clinical animal toxicity studies. The appendices specify the types of studies needed, such as single dose toxicity studies, repeated dose toxicity studies, reproductive toxicity studies, and carcinogenicity studies, along with the testing parameters and number of animals required for each.
alternative methods of animal toxicity.pptxashharnomani
Alternative methods to animal toxicity testing are needed because animal testing can cause suffering. Some alternative methods include computer modeling, cell and tissue cultures, and organ chips. Computer modeling uses computer programs to simulate biological effects and predict toxicity without animal testing. Cell and tissue cultures grow isolated cells and tissues in vitro to study toxicity. Organ chips are microfluidic devices that contain living cells arranged to simulate organ-level functions, allowing tests on human-relevant systems without whole animals. These alternative methods can help reduce and replace animal use in toxicity testing.
The document describes the hERG assay, which is used to test for potential drug-induced prolongation of the QT interval. It discusses the hERG gene and potassium channel, how mutations can cause long QT syndrome. It then summarizes three methods for conducting the hERG assay: electrophysiological assay using whole-cell patch clamping, Fluorometric imaging plate reader-based thallium flux assay, and radioligand binding with 35S-MK-499. Details are provided on cell preparation and protocol for each type of hERG assay.
Regulatory guidelines for conducting toxicity studies by ichAnimatedWorld
The document outlines regulatory guidelines for conducting toxicity studies established by the International Council on Harmonization (ICH). ICH provides guidelines on quality, safety, and efficacy for pharmaceutical registration. The safety guidelines cover areas like carcinogenicity studies, genotoxicity testing, toxicokinetics, duration of chronic toxicity testing, reproductive toxicity testing, immunotoxicity studies, phototoxicity evaluation, and nonclinical safety testing to support pediatric medicine development. Expert working groups establish the guidelines to ensure a consistent approach to nonclinical safety assessment is applied across regions.
The document provides an overview of the regulatory process for bringing a new drug to market, beginning with pre-clinical studies and submission of an Investigational New Drug (IND) application to the FDA. If approved, the IND allows clinical trials to be conducted in three phases to evaluate safety and efficacy. If phase 3 trials demonstrate a drug is safe and effective, a New Drug Application or Biologics License Application can be submitted for approval to market the drug. Ongoing monitoring of safety continues even after approval.
REPRODUCTIVE TOXICITY STUDIES, Definition
Introduction, OECD guidelines for reproductive toxicity studies
Principle of the test, Description of Method, Procedure, Experimental Schedule, Data and Reporting, Results, Male Fertility Toxicological Studies
Ms. I. Sai Reddemma.
Department of Pharmacology
Economics of drug discovery. final.pptxashharnomani
The document discusses the economics of drug discovery. It notes that drug discovery is a lengthy and expensive process, taking 3-20 years and costing billions of dollars. Key points include:
- Drug discovery involves identifying potential drug targets and compounds through research. Clinical trials then test compounds on animals and humans.
- Total R&D costs to bring a new drug to market were estimated at $985 million to $1.3 billion in 2020, though some prior estimates were as high as $2.8 billion.
- The majority of costs (40%) go towards clinical trials, with drug discovery and pre-clinical trials accounting for 30-50% of total costs. Failed drug candidates also contribute to overall costs.
The guidelines describe about the subacute toxicity studies in rodents with a comparison with the previous guideline.it also includes the comparison of all three subacute toxicity studies OECD 407, OECD 410, and OECD 412
Screening methods for skin sensitization, skin irritation and dermal toxicity...Ch. Bhargava krishna
This document discusses screening methods for skin sensitization, irritation, and toxicity studies. It describes the Guinea Pig Maximization Test and Buehler Test methods for assessing skin sensitization potential. The Local Lymph Node Assay is presented as a new alternative method that provides more objective data on sensitization potential. For skin irritation screening, the document outlines using rabbits as test subjects and applying a test chemical to the skin to evaluate the degree of irritation.
The document summarizes skin sensitization testing methods according to OECD Guideline 406. It describes two common animal models - the guinea pig and mouse - and tests used, including the Guinea Pig Maximization Test and Buehler Test. It provides details on study design, including number of animals, induction and challenge procedures, observations, and scoring of skin reactions. The goal is to screen substances for their potential to cause skin sensitization or allergic contact dermatitis in humans.
This document discusses safety pharmacology studies, with a focus on respiratory and central nervous system safety pharmacology. It defines safety pharmacology studies as investigating potential undesirable pharmacological effects of substances on physiological functions. For respiratory safety pharmacology, the core battery studies measure respiratory rate, tidal volume, and oxygen saturation. Supplementary studies measure airway resistance and lung compliance. For CNS safety pharmacology, core studies evaluate behavior, locomotor activity, motor coordination, and seizure liability. Safety pharmacology aims to identify risks and inform safe starting doses in clinical trials.
This document summarizes a seminar on safety pharmacology. It defines safety pharmacology and outlines the core battery of studies, which evaluate effects on the central nervous, cardiovascular and respiratory systems. It describes when safety pharmacology studies are needed at different stages of drug development and under various conditions. Guidelines for conducting the studies from organizations like ICH are also discussed.
The document discusses safety pharmacology studies that are conducted to evaluate potential adverse effects of pharmaceutical substances on vital organ systems. It describes the safety pharmacology core battery that investigates effects on the central nervous, cardiovascular and respiratory systems. Follow up studies provide more in-depth understanding of effects on these systems. Supplemental studies evaluate effects on other organ systems like renal, gastrointestinal and immune systems. A variety of evaluation methods are used like functional observation, electrocardiography, plethysmography and biomarkers. Conditions where safety pharmacology studies may not be needed are also outlined.
Safety pharmacology is a branch of pharmacology with its aim to predict the potential clinical risk profile of new chemical entities (NCEs).
It has the ability to predict the potential off-target drug effects on major organ systems which are associated with exposure in the therapeutic range and above.
As an essential part of the spectrum of drug discovery and development, safety pharmacology studies are generally conducted to determine the relative drug effect on main organs, including respiratory system, central nervous system, and cardiovascular system.Safety pharmacology is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials.
SP studies are described in the international conference on harmonization (ICH) S7A and S7B Guidelines.
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.
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
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.
Acute eye irritation OECD 405 m pharm cology 2nd sem..pptxPiyushZala5
This document provides guidelines for conducting an acute eye irritation test using rabbits according to OECD Test Guideline 405. It describes the test procedure which involves applying a test chemical to the eye of an anesthetized rabbit and observing it for signs of irritation over 21 days. Pain management for the rabbits involves pretreatment with anesthetics and post-treatment analgesics. Observations are made at specific time points to evaluate any eye reactions and determine if the chemical causes eye irritation.
Expt. 11 Determination of acute eye irritation corrosion of a test substanceVISHALJADHAV100
This document outlines the procedure for conducting an acute eye irritation/corrosion test of a substance using albino rabbits. The objective is to determine the degree of eye irritation or corrosion caused by a test substance. A single dose of the substance is applied to one eye of each rabbit, while the other eye serves as a control. Lesions to the conjunctiva, cornea, and iris are observed and graded at various time intervals over 72 hours. Based on the grading scores of the test eye compared to the control eye, the sensitization potential of the substance can be determined.
The document provides guidelines for conducting acute eye irritation/corrosion toxicity studies in animals. It outlines procedures to minimize pain including use of analgesics, anesthetics, and humane endpoints. Topical anesthetics should be applied before the test substance and systemic analgesics administered afterwards. Lesions are graded and animals showing severe signs of pain are euthanized. The duration allows for monitoring reversibility of effects while prioritizing animal welfare.
This document discusses ophthalmic diagnostic agents used to facilitate eye examinations and diagnoses. It outlines various classes of diagnostic agents including cycloplegics, mydriatics, anesthetics, and dyes. Cycloplegics induce paralysis of the ciliary muscles while mydriatics dilate the pupil. Anesthetics reversibly block nerve impulses along sensory fibers. Common diagnostic dyes include fluorescein and rose bengal which help identify ocular structures. The document discusses the mechanisms, indications, and side effects of various ophthalmic diagnostic agents.
Ophthalmic preparations can be solutions, suspensions, ointments or gels applied topically to the eye. Solutions are diluted with tears and drained quickly, while suspensions, ointments and gels have longer contact times. Various drugs are used depending on the condition, such as anti-infectives, anti-inflammatory corticosteroids or drugs for glaucoma. Considerations for ophthalmic formulations include ensuring sterility, controlling pH and tonicity, and using preservatives in multi-dose products. Packaging must also maintain sterility and be compatible with the formulation. Newer delivery systems aim to further prolong drug release for better treatment outcomes.
a emergency treatment of poisoning.describe of ingested poisons,inhaled poisons,absorbed poison,food poisoning,injected poisoning,snake bite. management of treatment
The document discusses parenteral preparations, which are sterile preparations intended for administration by injection, infusion, or implantation. They contain one or more active ingredients and are packaged in single-dose or multidose containers. The document outlines various aspects of parenteral preparations, including definitions, routes of administration, formulation components, evaluation tests, and sterilization methods.
Ocular allergy are a group of external ocular conditions resulting from one or more types of hypersensitivity reactions to allergens.
Anti Allergic eye drops are liquid medicine used to treat symptoms of eye allergies.
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.
The document discusses procedures for eye irrigation, eye drops, and ear irrigation including their purposes, indications, contraindications, complications, principles, guidelines, and the nurse's responsibilities before, during, and after each procedure with the goal of providing concise information on performing and assisting with these common clinical skills.
The document discusses OECD Guideline 423 for acute oral toxicity testing. It outlines that the guideline uses a stepwise testing process with only 3 animals per step to classify chemicals according to their toxicity while minimizing animal use. The testing involves observing animals for signs of toxicity after administering chemical doses and determining subsequent dose levels based on mortality responses. The goal is to classify chemicals according to the globally harmonized system to improve knowledge of hazardous chemicals.
The document discusses OECD Guideline 423 for acute oral toxicity testing. It outlines that the guideline uses a stepwise testing process with only 3 animals per step to classify chemicals according to their toxicity while minimizing animal use. The testing involves observing animals for signs of toxicity after administering chemical doses and determining subsequent dose levels based on mortality responses. The goal is to classify chemicals according to the globally harmonized system to improve knowledge of hazardous chemicals.
DERMAL IRRITATION STUDY ACCORDING TO OECD(404) GUIDELINESMO.SHAHANAWAZ
This document summarizes a dermal irritation study conducted according to OECD guidelines using rabbits. It describes procedures for handling, restraining, and housing the rabbits, as well as applying the test chemical to their skin for 4 hours. Observations are made at several time points over 14 days to evaluate the degree of irritation or corrosion and reversibility of any effects. Scoring is based on criteria for erythema, edema, and other reactions. The study aims to safely and humanely evaluate the skin toxicity of chemicals.
Anlalgesic activity and its classificationKOMAL AROOSH
Analgesics are medicines that are used to relieve pain. They are also known as painkillers or pain relievers. Technically, the term analgesic refers to a medication that provides relief from pain without putting you to sleep or making you lose consciousness.
This document discusses occupational health hazards faced by nurses from exposure to chemicals, including chemotherapeutic drugs. It notes that nurses are at risk of various health issues from regular exposure to sterilizing agents, disinfectants, anesthetic gases, and antineoplastic drugs used in chemotherapy. Precautions like proper use of personal protective equipment, ventilation, limiting exposure times, and hygiene practices can help reduce risks. However, studies show nurses still experience high rates of injury from improper protective measures or lack of awareness regarding chemical hazards of their work environment.
The document discusses drugs acting on the eye, ear, and nose. It provides details on common eye, ear, and nasal conditions and the drug classes used to treat them. For the eye, it describes ophthalmic antibiotics, anti-inflammatory drugs, miotics, and mydriatics used for issues like infection, inflammation, glaucoma, and dry eye. For the ear, it discusses antibiotics, anti-inflammatory, and wax softening drugs used for otitis media and externa. Nasal drops containing pseudoephedrine and saline are used for nasal allergy and congestion relief.
The document contains a repeated link to the website https://www.ctevtnote.com without any other text, images or context. It appears to be promoting this single website through numerous repetitions of its URL address.
gene mapping, clonning of disease gene(1).pptxRajesh Yadav
1) The document discusses gene mapping, cloning of disease genes, and genetic variation in drug transporters. It provides details on techniques for gene mapping like genetic mapping and physical mapping.
2) Key points about cloning disease genes include using gene mapping to identify disease-causing genes, and two approaches for cloning genes - for genes of known function and unknown function.
3) The document also discusses genetic variation in drug transporter proteins like ABC transporters and solute carrier proteins, how polymorphisms can affect drug disposition and response.
This document provides information on genomics, proteomics, and metabolomics. It discusses that genomics is the study of genomes through sequencing and analysis. It involves various types of genomics like structural, functional, and comparative genomics. Proteomics is the large-scale study of the structure and function of proteins in organisms. Key proteomics methods include antibody detection and mass spectrometry. Metabolomics is the study of small molecule metabolites within cells and biofluids, which make up the metabolome. These "omics" fields provide insights into cellular processes and are applied in areas like disease diagnosis and drug development.
This document provides an overview of immunoassays including radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA). It discusses the principles, types, and applications of immunoassays. Key points include: immunoassays use the specific binding of antibodies and antigens to detect analytes, RIA uses radioisotopes providing high sensitivity but potential hazards, ELISA uses enzyme reactions and is safer and more versatile than RIA, and common applications of immunoassays include detecting hormones, drugs, and infectious agents.
This document provides an overview of electrophoresis, including its principle, working conditions, factors affecting separation, and types. Electrophoresis is an analytical technique that separates charged molecules like proteins and nucleic acids based on their movement in an electric field. It works by applying a voltage to move molecules through a buffer solution or gel support medium. The rate of migration depends on factors like the molecule's charge, size, and the electric field strength. Common electrophoresis techniques described include zone electrophoresis using paper, gels, and thin layers, as well as moving boundary methods like capillary electrophoresis.
Evaluation of the Anxiolytic Activity of Ethanolic Extract of Galinsoga parvi...Rajesh Yadav
The document describes a study that evaluated the anxiolytic (anti-anxiety) activity of the ethanolic extract of Galinsoga parviflora in mice models. Mice were orally administered doses of the Galinsoga parviflora extract or diazepam and tested in the light-dark box, hole board, and rotarod tests. The extract at a dose of 200 mg/kg significantly increased the time mice spent in the light box and the number of head dips in the hole board test, similar to diazepam. The extract did not impair motor coordination on the rotarod test like diazepam did. The results provide support for the anxiolytic effects of
1. The document summarizes the different types of hypersensitivity reactions: immediate (types I-III) and delayed (type IV). Immediate reactions occur within seconds to minutes after antigen exposure and involve antibody-mediated responses. Delayed reactions occur 24-48 hours after exposure and involve T cell-mediated responses.
2. Type I reactions are anaphylactic and mediated by IgE antibodies binding to mast cells and basophils. Type II reactions are antibody-mediated and cytotoxic, targeting cell surface antigens. Type III reactions involve immune complex deposition and complement activation, causing tissue injury. Type IV reactions are delayed hypersensitivity responses mediated by T cells without antibody formation.
There are several types of adverse drug reactions:
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1. ADITYA INSTITUTE OF PHARMACY
DEPARTMENT OF PHARMACOLOGY
PHARMACOLOGICAL AND TOXICOLOGICAL SCREENING METHOD
PRESENTATION ON
Acute eye irritation , skin sensitization and dermal toxicity
SUBMITED TO: DR. N.VENKATESAN
Submitted by ,
RAJESH YADAV
2. UNIT 2
TOXICOLOGICAL SCREENING METHODS
OBJECTIVE
1 Acute eye irritation and skin sensitization.
Irritation,
in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-
lining damage. A stimulus or agent which induces the state of irritation is an
irritant.
Irritants are typically thought of as chemical agents (for example phenol and capsaicin) but
mechanical, thermal (heat), and radiative stimuli (for example ultraviolet light or ionising
radiations) can also be irritants. Irritation also has non-clinical usages referring to bothersome
physical or psychological pain or discomfort.
Irritation can also be induced by some allergic response due to exposure of some allergens for
example contact dermatitis, irritation of mucousal membranes and pruritus. Mucosal
membrane is most common site of irritation because it contains secretory glands that release
mucous which attracts the allergens due to its sticky nature.
Chronic irritation is a medical term signifying that afflictive health conditions have been
present for a while. There are many disorders that can cause chronic irritation, the majority
involves the skin, vagina, eyes and lungs.
Types of irritation
1 eye irritation
2 skin irriatation
3vaginal irritation
4 stomach irritation
Eye irritation
Infant with blepharitis on the right eye
Modern office work with use of office equipment has raised concerns about possible adverse
health effects.[1] Since the 1970s, reports have linked mucosal, skin, and general symptoms to
work with self-copying paper. Emission of various particulate and volatile substances has
been suggested as specific causes. These symptoms have been related to Sick Building
3. Syndrome, which involves symptoms such as irritation to the eyes, skin, and upper airways,
headache and fatigue.[2]
The eye is also a source of chronic irritation. Disorders like Sjögren's syndrome, where one
does not make tears, can cause a dry eye sensation which feels very unpleasant. The
condition is difficult to treat and is lifelong. Besides artificial tears, there is a drug called
Restasis which may help.[3]
Blepharitis is dryness and itching on the upper eyelids. This condition is often seeing in
young people and can lead to reddish dry eye and scaly eyebrows. To relieve the itching
sensation, one may need to apply warm compresses and use topical corticosteroid creams.
Acute eye irritation/corrosion- 405
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.
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.
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
4. 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.
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.
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.
“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
5. 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.
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.
(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.
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
6. 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.
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.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:
i. corneal perforation or significant corneal ulceration including staphyloma;
ii. blood in the anterior chamber of the eye.
iii. grade 4 corneal opacity.
iv. absence of a light reflex (iridial response grade 2) which persists for 72 hours;
v. ulceration of the conjunctival membrane;
vi. necrosis of the conjunctivae or nictitating membrane; or sloughing.
vii. 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
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
7. other suitable device. After recording the observations at 24 hours, the eyes may be further
examined with the aid of fluorescein.
Skin sensitization
skin sensitisers are substances able to elicit an allergic response following contact with the
skin, termed allergic contact dermatitis (ACD) in humans.
INTRODUCTION
1. OECD Guidelines for Testing of Chemicals are periodically reviewed in light of scientific
progress. In such reviews, special attention is given to possible improvements in relation to
animal welfare. This updated version of the original guideline 406, adopted in 1981, is the
outcome of a meeting of OECD experts held in Paris in May 1991.
2. Currently, quantitative structure-activity relationships and in vitro models are not yet
sufficiently developed to play a significant role in the assessment of the skin-sensitisation
potential of substances which therefore must continue to be based on in vivo models.
3. The guinea pig has been the animal of choice for predictive sensitisation tests for several
decades. Two types of tests have been developed: adjuvant tests in which sensitisation is
potentiated by the injection of Freunds Complete Adjuvant (FCA), and non-adjuvant tests. In
the original guideline 406, four adjuvant tests and three non-adjuvant tests were considered to
be acceptable. In this updated version, the Guinea Pig Maximisation Test (GPMT) of
Magnusson and Kligman which uses adjuvant (1)(2)(3)(4) and the non-adjuvant Buehler Test
(5)(6) are given preference over other methods and the procedures are presented in detail. It is
recognised, however, that there may be circumstances where other methods may be used to
provide the necessary information on sensitisation potential.
GENERAL PRINCIPLE OF SENSITISATION TESTS IN GUINEA PIGS
6. The test animals are initially exposed to the test substance by intradermal injection and/or
epidermal application (induction exposure). Following a rest period of 10 to 14 days
(induction period), during which an immune response may develop, the animals are exposed
to a challenge dose. The extent and degree of skin reaction to the challenge exposure in the
test animals is compared with that demonstrated by control animals which undergo sham
treatment during induction and receive the challenge exposure
ELEMENTS COMMON TO SENSITISATION TESTS IN GUINEA PIGS
Sex of animals
7. Male and/or female healthy young adult animals can be used. If females are used they
should be nulliparous and non-pregnant.
Housing and feeding conditions
8. 8. The temperature of the experimental animal room should be 20oC (+ 3oC) and the relative
humidity 30-70 per cent. Where the lighting is artificial, the sequence should be 12 hours
light, 12 hours dark. For feeding, conventional laboratory diets may be used with an
unlimited supply of drinking water. It is essential that guinea pigs receive an adequate
amount of ascorbic acid.
Preparation of the animals
9. Animals are acclimatised to the laboratory conditions for at least 5 days prior to the test.
Before the test, animals are randomised and assigned to the treatment groups. Removal of
hair is by clipping, shaving or possibly by chemical depilation, depending on the test method
used. Care should be taken to avoid abrading the skin. The animals are weighed before the
test commences and at the end of the test.
Reliability check
10. The sensitivity and reliability of the experimental technique used should be assessed
every six months by use of substances which are known to have mild-to-moderate skin
sensitisation properties.
11. In a properly conducted test, a response of at least 30% in an adjuvant test and at least
15% in a non-adjuvant test should be expected for mild/moderate sensitisers. Preferred
substances are hexyl cinnamic aldehyde (CAS No. 101-86-0), mercaptobenzothiazole (CAS
No. 149-30-4) and benzocaine (CAS No. 94-09-7). There may be circumstances where, given
adequate justification, other control substances meeting the above criteria may be used
Removal of the test substance
12. If removal of the test substance is considered necessary, this should be achieved using
water or an appropriate solvent without altering the existing response or the integrity of the
epidermis
DESCRIPTION OF THE GUINEA-PIG MAXIMISATION TEST METHOD
Number of animals
13. A minimum of 10 animals is used in the treatment group and at least 5 animals in the
control group. When fewer than 20 test and 10 control guinea pigs have been used, and it is
not possible to conclude that the test substance is a sensitiser, testing in additional animals to
give a total of at least 20 test and 10 control animals is strongly recommended.
Dose levels
14. The concentration of test substance used for each induction exposure should be well-
tolerated systemically and should be the highest to cause mild-to-moderate skin irritation.
The concentration used for the challenge exposure should be the highest non-irritant dose.
The appropriate concentrations can be determined from a pilot study using two or three
animals. Consideration should be given to the use of FCA-treated animals for this purpose.
Induction: Intradermal Injections
9. Day 0 - treated group
15. Three pairs of intradermal injections of 0.1 ml volume are given in the shoulder region
which is cleared of hair so that one of each pair lies on each side of the midline.
Injection 1: a 1:1 mixture (v/v) FCA/water or physiological saline
Injection 2: the test substance in an appropriate vehicle at the selected concentration
Injection 3: the test substance at the selected concentration formulated in a 1:1 mixture
(v/v) FCA/water or physiological saline.
16. In injection 3, water soluble substances are dissolved in the aqueous phase prior to mixing
with FCA. Liposoluble or insoluble substances are suspended in FCA prior to combining
with the aqueous phase. The concentration of test substance shall be equal to that used in
injection 2.
17. Injections 1 and 2 are given close to each other and nearest the head, while 3 is given
towards the caudal part of the test area.
Day 0 - control group
18. Three pairs of intradermal injections of 0.1 ml volume are given in the same sites as in the
treated animals.
Injection 1: a 1:1 mixture (v/v) FCA/water or physiological saline
Injection 2: the undiluted vehicle
Injection 3: a 50% w/v formulation of the vehicle in a 1:1 mixture (v/v) FCA/water or
physiological saline.
Induction: Topical Application
Day 5-7 - treated and control groups
19. Approximately twenty-four hours before the topical induction application, if the
substance is not a skin irritant, the test area, after close-clipping and/or shaving is painted
with 0.5 ml of 10% sodium lauryl sulphate in vaseline, in order to create a local irritation.
Day 6-8 - treated group
20. The test area is again cleared of hair. A filter paper (2 x 4 cm) is fully-loaded with test
substance in a suitable vehicle and applied to the test area and held in contact by an occlusive
dressing for 48 hours. The choice of the vehicle should be justified. Solids are finely
incorporated in a suitable vehicle. Liquids can be applied undiluted, if appropriate.
Day 6-8 - control group
10. 21. The test area is again cleared of hair. The vehicle only is applied in a similar manner to
the test area and held in contact by an occlusive dressing for 48 hours.
Challenge: Topical Application
Day 20-22 - treated and control groups
22. The flanks of treated and control animals are cleared of hair. A patch or chamber loaded
with the test substance is applied to one flank of the animals and, when relevant, a patch or
chamber loaded with the vehicle only may also be applied to the other flank. The patches are
held in contact by an occlusive dressing for 24 hours.
Observations -treated and control groups
23. - approximately 21 hours after removing the patch the challenge area is cleaned and
closely-clipped and/or shaved or depilated if necessary;
- approximately 3 hours later (approximately 48 hours from the start of the challenge
application) the skin reaction is observed and recorded according to the grades shown below;
- approximately 24 hours after this observation a second observation (72 hours) is made and
once again recorded.
Blind reading of test and control animals is encouraged.
TABLE: MAGNUSSON AND KLIGMAN GRADING SCALE FOR THE
EVALUATION
OF CHALLENGE PATCH TEST REACTIONS
0 = no visible change
1 = discrete or patchy erythema
2 = moderate and confluent erythema
3 = intense erythema and swelling
Rechallenge
24. If it is necessary to clarify the results obtained in the first challenge, a second challenge
(i.e. a rechallenge), where appropriate with a new control group, should be considered
approximately one week after the first one. A rechallenge may also be performed on the
original control group.
Clinical observations
25. All skin reactions and any unusual findings, including systemic reactions, resulting from
induction and challenge procedures should be observed and recorded. Other procedures, e.g.
11. DESCRIPTION OF THE BUEHLER TEST METHOD
Number of animals
26. A minimum of 20 animals is used in the treatment group and at least 10 animals in the
control group.
Dose levels 27. The concentration of test substance used for each induction exposure should
be the highest to cause mild irritation. The concentration used for the challenge exposure
should be the highest non-irritating dose. The appropriate concentration can be determined
from a pilot study using two or three animals.
28. For water soluble test materials, it is appropriate to use water or a dilute non-irritating
solution of surfactant as the vehicle. For other test materials 80% ethanol/water is preferred
for induction and acetone for challenge
Topical application
Day 0 - treated group
29. One flank is cleared of hair (closely-clipped). The test patch system should be fully
loaded with test substance in a suitable vehicle (the choice of the vehicle should be justified;
liquid test substances can be applied undiluted, if appropriate). The test patch system is
applied to the test area and held in contact with the skin by an occlusive patch or chamber and
a suitable dressing for 6 hours.
30. The test patch system must be occlusive. A cotton pad is appropriate and can be circular
or square, but should approximate 4-6 cm2. Restraint using an appropriate restrainer is
preferred to assure occlusion. If wrapping is used, additional exposures may be required.
Day 0 - control group
31. One flank is cleared of hair (closely-clipped). The vehicle only is applied in a similar
manner to that used for the treated group. The test patch system is held in contact with the
skin by an occlusive patch or chamber and a suitable dressing for 6 hours. If it can be
demonstrated that a sham control group is not necessary, a naive control group may be used.
Observations -treated and control groups
34. - approximately 21 hours after removing the patch the challenge area is cleared of hair;
- approximately three hours later (approximately 30 hours after application of the challenge
patch) the skin reactions are observed and recorded according to the grades shown in the
Guinea-Pig Maximisation Test (see paragraph 23);
- approximately 24 hours after the 30 hour observation (approximately 54 hours after
application of the challenge patch) skin reactions are again observed and recorded.
Blind reading of test and control animals is encouraged
12. Rechallenge
35. If it is necessary to clarify the results obtained in the first challenge, a second challenge
(i.e. a rechallenge), where appropriate with a new control group, should be considered
approximately one week after the first one. The rechallenge may also be performed on the
original control group.
Clinical observations
36. All skin reactions and any unusual findings, including systemic reactions, resulting from
induction and challenge procedures should be observed and recorded. Other procedures, e.g.
histopathological examination, measurement of skin fold thickness, may be carried out to
clarify doubtful reactions.
DATA AND REPORTING
13.
14.
15.
16. DERMAL TOXICOLOGY
Introduction
Dermal toxicity, also known as cutaneous toxicity is the ability of a substance to poison
people or animals by contact with the skin. Toxic materials absorb through the skin to various
degrees depending on their chemical composition and whether they are dissolved in a solvent.
Occupational skin diseases are the second most common types of occupational disease.
Greatest number of occupational skin disease cases occur in the agricultural and
manufacturing industries
Functions of Skin
Environmental barrier
Diffusion barrier
Metabolic Barrier
Mechanical Support
Neurosensory Reception
Physiologically, Skin Participates Directly In
Thermal Regulation
Regulation Of Blood Flow, Hair And Fur, Sweating
Metabolism
Keratin, Collage, Melanin, Lipids, And Vitamin D Synthesis, Respiration And
Biotransformation
Electrolyte And Hormonal Regulation
Apocrine/Eccrine/Sebaceous Glandular Secretion
17. Manifestation
Contact Dermatitis
Allergic Contact Dermatitis
Ulcers
Utricaria
Toxic Epidermal Necrolysis
Acneiform Dermatoses
Pigment Disturbances
Photosensitivity
Skin Cancer
Contact Dermatitis
Irritant contact dermatitis is one of the most common occupational diseases. is confined to
the area of irritant exposure. Symptoms are hives (wheals), reddening of the skin (erythema),
blistering, eczemas or rashes that weep and ooze, hyperkeratosis (thickening of the skin),
pustules, and dryness and roughness of the skin. Treatment is by reducing or avoiding the
amount of exposure to the irritant. Wearing gloves to provide protection against wetness or
chemicals and minimizing wet working conditions and hand washing can be very helpful.
Extremely corrosive and reactive chemicals can cause immediate coagulative necrosis at the
site of contact resulting in substantial tissue damage. These are called primary irritants that
cause nonselective damage at the site of contact & also causes damage resulting from their
reactivity, such as acids precipitating proteins and solvents dissolving cell membranes, both
resulting in cell damage, death, or disruption of the keratin ultrastructure.
18. Allergic Contact Dermatitis
Allergic contact dermatitis is a delayed type IV hypersensitivity reaction that is mediated by
a triggered immune response. On first exposure to the allergenic chemical, little or no
response occurs. After this first exposure, the individual becomes sensitized to the chemical,
and subsequent exposures elicit the typical delayed type IV hypersensitivity reaction. The
allergenic agents (haptens) are typically low-molecular-weight chemicals that are
electrophilic or hydrophilic. These agents are seldom allergenic alone and must be linked
with a carrier protein to form a complete allergen. Some chemicals must be metabolically
activated in order to form an allergen. Patch testing is used to try to determine to which agent
a person with suspected allergic contact dermatitis may be sensitive. The best treatment,
however, is avoidance of the allergen or irritant. Baths and wet compresses, antibiotics,
antihistamines, and corticosteroids are used in various combinations to treat contact
dermatitis.
Ulcers
Some chemicals can cause ulceration of the skin. This involves sloughing of the epidermis
and damage to the exposed dermis. Ulcers are commonly triggered by acids, burns, and
trauma and can occur on mucous membranes and the skin. Two commonly encountered
compounds that induce ulcers are cement and chrome.
Utricaria
Triggered by immunity-related mechanisms, and minute quantities of allergen. Urticaria
results in the typical hives, which are pruritic red wheals that erupt on the skin. Asthma is
also a common occurrence after exposure to an inducer of urticaria. The symptoms often last
less than 24 h. In severe cases, however, anaphylaxis and/or death may occur. Most
compounds that induce urticaria must enter the systemic circulation. Some potential
nonimmune inducers of urticaria are curare, aspirin, azo dyes, and toxins from plants and
animals. A smaller number of agents may cause contact urticaria on exposure only to the
epidermis. Cobalt chloride, benzoic acid, butylhydroxyanisol (BHA), and methanol have
been reported to cause this form of urticaria. One of the most common inducers of contact
urticaria seen in the medical community is caused by latex rubber products such as gloves.
Toxic Epidermal Necrolysis
Toxic epidermal necrolysis (TEN) is one of the most immediate lifethreatening skin diseases
caused by chemicals or drugs. The disease is characterized by a sudden onset of large, red,
tender areas involving a large percentage of the total body surface area. As the disease
progresses, necrosis of the epidermis with widespread detachment occurs at the affected
areas. Once the epidermis is lost, only the dermis remains, severely compromising the ability
of the skin to regulate temperature, fluid, and electrolyte homeostasis. Since the epidermis is
lost, the remaining dermis posses little resistance to chemicals entering the systemic
circulation and to infection from microorganisms.
Acneiform Dermatoses
Acne is a very disfiguring ailment & the most common causes of acne are petroleum, coal
tar, and cutting oil products. They are termed comedogenic since they induce the
characteristic comedo, which is either open (blackhead) or closed (whitehead). The
19. comedogenic agents produce biochemical and physiological alterations in the hair follicle and
cell structure that cause accumulation of compacted keratinocytes in the hair follicles and
sebaceous glands. The keratinocytes clog the hair follicles and sebaceous glands.
Halogenated chemicals as polyhalogenated naphthalenes, biphenyls, dibenzofurans,
polychlorophenol and dichloroaniline—cause a very disfiguring and recalcitrant form of acne
called chloracne. It is typically characterized by the presence of many comedones and straw-
colored cysts behind the ears, around the eyes, and on the shoulders, back, and genitalia. To
prevent exposure to the halogenated chemicals could involve putting up splash guards and
other devices to prevent the chemicals from coming into contact with the skin along with
changing chemical soaked clothing frequently
Pigment Disturbances
Some chemicals can cause either an increase or decrease in pigmentation. These compounds
often cause hyperpigmentation (darkening of the skin) by enhancing the production of
melanin or by causing deposition of endogenous or exogenous pigment in the upper
epidermis. Hypopigmentation (loss of pigment from the skin) can be caused by decreased
melanin production and/or loss, melanocyte damage, or vascular abnormalities. Some
common hyperpigment inducers are coal tar compounds, metals (e.g., mercury, lead, arsenic),
petroleum oils, and a variety of drugs. Phenols and catechols are potent depigmentors that act
by killing melanocytes.
Photosensitivity
Photosensitivity is an abnormal sensitivity to ultraviolet (UV) and visible light and can be
caused by endogenous and exogenous factors. Chromophores, epidermal thickness, and water
content all affect the ability of light to penetrate the skin, and those parameters vary from
region to region on the body. Melanin is the most significant chromophore, since it can
absorb a wide range of radiation from UVB (290–320 nm) through the visible spectrum.
Exposure to intense sunlight causes erythema. Inflammatory mediators may be released at
these areas and have been implicated in the systemic symptoms of sunburn such as fever,
chills, and malaise. UVB is the most important radiation band in causing erythema. Ionizing
radiation can cause acute changes such as redness, blistering, swelling, ulceration, and pain.
Following a latent period or chronic exposure, epidermal thickening, freckling, nonhealing
ulcerations, and malignancies may occur. and chemicals. Photoallergy is very similar to
contact allergic dermatitis and is a delayed type IV hypersensitivity reaction. The difference
between an allergenic chemical and a photoallergenic chemical is that the photoallergenic
chemical must be activated by exposure to light—most often UVA.
Skin Cancer
Skin cancer is the most common neoplasm in humans with half a million new cases
occurring per year in the United States. Even though exposure to UV light is the primary
cause of skin cancer, chemicals can also induce malignancies. UV light and carcinogenic
agents induce alterations in epidermal cell DNA. These alterations can lead to permanent
mutations in critical genes that cause uncontrolled proliferation of the affected cells,
ultimately leading to a cancerous lesion. Since UVB light is the most potent inducer of DNA
damage, utilization of a sunscreen that blocks UVB radiation is critical in preventing skin
cancer along with the other skin effects associated with UV light exposure. The best