Studies on general toxicity include acute, sub-acute, sub-chronic, and chronic toxicity studies to determine the effects of repeated exposure to a chemical over different time periods. Developmental and reproductive toxicity studies evaluate effects on fertility, pregnancy, and offspring. Mutagenicity studies test whether chemicals cause genetic mutations. Carcinogenicity studies involve long-term exposure of rodents to assess cancer potential. Immunotoxicity assessment evaluates impacts on the immune system.
The document provides information on chronic toxicity studies as outlined in OECD Test Guideline 452. It discusses that chronic toxicity studies involve administering test substances to animals daily for over 90 days, typically 12 months, to identify target organs and dose-response relationships. The test substance is given orally, dermally, or via inhalation to groups of rodents like rats or mice, with at least 20 animals of each sex per dose group. Animals are observed closely for signs of toxicity and may be killed at interim periods or after 12 months for examination.
Experimental Techniques For Evaluation Of New Drugs.pptKarabiAdak
Experimental techniques are used to evaluate new drugs for toxicity, efficacy, and safety prior to human clinical trials. This includes acute and chronic toxicity studies in two animal species to identify target organ toxicity and establish a maximum tolerated dose. Genotoxicity and carcinogenicity studies are also conducted to assess genetic damage and cancer risk. Alternative methods seek to reduce animal testing through computer models, cell cultures, and organ-specific assays.
Chronic toxicity studies are conducted over a long period of time, usually 12 months, to determine the effects of repeated exposure to a substance. They are guided by organizations like OECD and involve observations of animals dosed with the substance over their lifetime. Key steps include dosing animals at different levels and observing them for signs of toxicity, conducting clinical pathology tests, and examining organs at necropsy. The results are reported and discuss dose-response relationships and any target organs affected to understand the substance's chronic toxicity.
Pre-clinical screening involves testing potential new drugs in animal models before human trials to evaluate safety and efficacy. This includes pharmacological screening to determine mechanism of action and dose response, as well as toxicological testing to identify adverse effects and calculate safe starting doses for clinical trials. Studies progress from molecular and cellular assays to whole animal experiments. Acute and repeated dose toxicity tests are followed by sub-chronic and chronic studies to identify long-term effects. These pre-clinical studies aim to generate data required to deem a new compound safe enough for initial human testing.
Toxicity studies in animals are conducted to identify any toxic effects of a substance prior to clinical use in humans. The document outlines various types of toxicity studies including acute, subacute, chronic, and lethality studies. Acute studies involve a single high dose to determine toxic effects over 14 days, while repeated dose studies like subacute and chronic studies administer multiple lower doses over weeks to years to identify target organ toxicity. Lethality studies determine the lethal dose for 50% of animals (LD50). Systemic toxicity parameters evaluated include effects on liver, kidney, heart and other organs. Toxicity studies provide safety information required for approval to conduct human clinical trials.
A chronic toxicology study provides inferences about the long-term effect of a test substance in animals, and it may be extrapolated to the human safety of the test substance
This presentation is about toxic effects of different drugs and also how to reduce to its effect.
I hope you will like it,,
Don't forget to remember in your precious Dua,,
The document provides information on chronic toxicity studies as outlined in OECD Test Guideline 452. It discusses that chronic toxicity studies involve administering test substances to animals daily for over 90 days, typically 12 months, to identify target organs and dose-response relationships. The test substance is given orally, dermally, or via inhalation to groups of rodents like rats or mice, with at least 20 animals of each sex per dose group. Animals are observed closely for signs of toxicity and may be killed at interim periods or after 12 months for examination.
Experimental Techniques For Evaluation Of New Drugs.pptKarabiAdak
Experimental techniques are used to evaluate new drugs for toxicity, efficacy, and safety prior to human clinical trials. This includes acute and chronic toxicity studies in two animal species to identify target organ toxicity and establish a maximum tolerated dose. Genotoxicity and carcinogenicity studies are also conducted to assess genetic damage and cancer risk. Alternative methods seek to reduce animal testing through computer models, cell cultures, and organ-specific assays.
Chronic toxicity studies are conducted over a long period of time, usually 12 months, to determine the effects of repeated exposure to a substance. They are guided by organizations like OECD and involve observations of animals dosed with the substance over their lifetime. Key steps include dosing animals at different levels and observing them for signs of toxicity, conducting clinical pathology tests, and examining organs at necropsy. The results are reported and discuss dose-response relationships and any target organs affected to understand the substance's chronic toxicity.
Pre-clinical screening involves testing potential new drugs in animal models before human trials to evaluate safety and efficacy. This includes pharmacological screening to determine mechanism of action and dose response, as well as toxicological testing to identify adverse effects and calculate safe starting doses for clinical trials. Studies progress from molecular and cellular assays to whole animal experiments. Acute and repeated dose toxicity tests are followed by sub-chronic and chronic studies to identify long-term effects. These pre-clinical studies aim to generate data required to deem a new compound safe enough for initial human testing.
Toxicity studies in animals are conducted to identify any toxic effects of a substance prior to clinical use in humans. The document outlines various types of toxicity studies including acute, subacute, chronic, and lethality studies. Acute studies involve a single high dose to determine toxic effects over 14 days, while repeated dose studies like subacute and chronic studies administer multiple lower doses over weeks to years to identify target organ toxicity. Lethality studies determine the lethal dose for 50% of animals (LD50). Systemic toxicity parameters evaluated include effects on liver, kidney, heart and other organs. Toxicity studies provide safety information required for approval to conduct human clinical trials.
A chronic toxicology study provides inferences about the long-term effect of a test substance in animals, and it may be extrapolated to the human safety of the test substance
This presentation is about toxic effects of different drugs and also how to reduce to its effect.
I hope you will like it,,
Don't forget to remember in your precious Dua,,
General toxicology testing refers to a series of toxicity tests required by international regulators to prove safety in experimental animals prior to human testing. It includes acute, sub-acute, and chronic toxicity tests conducted according to OECD guidelines in rodents and non-rodents. Preclinical studies include phytochemistry, formulation development, pharmacology/pharmacokinetic profiling, safety toxicology studies, and efficacy studies. Toxicology studies are guided by regulatory requirements like OECD/ICH guidelines and Good Laboratory Practices to ensure quality. Acute, sub-acute, and chronic toxicity tests provide information on toxicity effects from single or repeated substance exposure over different time periods and help determine safe doses for clinical trials.
Toxicological Approach to Drug DiscoverySuhas Reddy C
This document outlines the toxicological approach to drug development. It discusses the importance of conducting various toxicity studies at different stages of drug development to ensure safety. These include single dose, repeated dose, fertility, reproductive, developmental and genotoxicity studies in animals. It describes the typical safety program involving staged approach and discusses factors to consider in designing toxicity studies. The goal is to obtain sufficient non-clinical safety data to support clinical trials and assess safety for human use.
Animal toxicity study requirements for conduct of clinical trial april 13 2019Akanksha William
This document provides guidance on conducting various types of animal toxicity studies required for clinical trials. It describes the objectives and key aspects of acute, repeated-dose, reproductive, and local toxicity studies. Acute toxicity studies in rodents aim to identify a safe starting dose for clinical studies. Repeated-dose studies in rodents and non-rodents over 14-180 days are used to identify target organ toxicity. Reproductive toxicity studies evaluate effects on fertility and development. Local toxicity studies assess hazards from dermal, ocular, or other routes of exposure. The document emphasizes standardized methods and selection of doses and species.
This document provides an overview of acute toxicity studies and OECD test guidelines for assessing acute oral toxicity. It discusses the principles and procedures for acute oral toxicity fixed dose tests per OECD Guideline 420. Key points include:
- Guideline 420 is an alternative to the conventional acute toxicity test that uses fewer animals and causes less suffering
- It involves dosing groups of animals with fixed doses (e.g. 5, 50, 300, 2000 mg/kg) and observing any signs of toxicity or mortality
- A sighting study is conducted to determine the starting dose for the main study
- Multiple animals are tested at each dose level in the main study with observation periods to monitor for any toxic effects
This document discusses various types of animal toxicity studies that are required before a drug can be administered to humans. It describes how these studies help establish the therapeutic index and predict adverse effects in humans. The key types of studies mentioned are systemic toxicity studies (including single dose, repeated dose, reproductive, and local toxicity), allergenicity/hypersensitivity studies, genotoxicity studies, and carcinogenicity/oncogenicity studies. Each type of study has specific objectives, test models used, parameters evaluated, and methods for conducting the studies and evaluating results. The studies aim to assess benefits and risks of drugs and establish their safety profiles before human use.
This document discusses various types of toxicology studies including acute, subacute, subchronic, and chronic toxicity studies. It provides definitions and describes the purpose and procedures for single dose acute toxicity testing of pharmaceuticals in animals. Classification criteria for substances based on exposure route and dose are presented. The document outlines observations, chronic toxicity studies, and principles of toxicity studies including following standard procedures and protecting animal welfare. Proposals for clinical studies include assessing drug exposure, plasma protein binding, metabolism, dose schedules, temporal relationships, and target engagement.
This document discusses principles of animal toxicology, including acute, subacute, and chronic toxicity testing. It defines key terms like toxicology, describes how drugs can cause toxicity, and explains different types of toxicity studies used to characterize a drug's safety profile. These include acute toxicity studies assessing effects of a single high dose, subacute studies examining impacts of repeat dosing over 14-28 days, and chronic studies evaluating long-term or lifetime exposure. The document also discusses LD50 values and how toxicology studies relate to pharmacology and clinical trials in the drug development process.
This document discusses the goals and requirements for preclinical safety and toxicity testing of new drug candidates. The primary goals are to estimate a safe starting dose for clinical trials, identify potential target organs of toxicity, and assess hazards that cannot be evaluated in clinical trials, like carcinogenicity. A variety of toxicity studies are required, including acute, repeated-dose, reproductive, and local toxicity studies. These studies must be conducted in two animal species, typically rats and non-rodents like dogs, and follow standardized guidelines for factors like number of animals, dose levels, routes of administration, duration and evaluation parameters. The results inform the design of subsequent clinical trials in humans.
This document discusses various types of animal toxicity studies conducted prior to clinical use of drugs in humans. It provides objectives and details of reproductive and developmental toxicity studies, local toxicity studies, carcinogenicity studies, and genotoxicity studies. Reproductive toxicity studies examine effects on fertility and development in offspring. Developmental toxicity studies evaluate effects during pregnancy and across lifespan. Local toxicity studies are required when drugs are administered via non-oral routes. Carcinogenicity studies identify substances that may induce or increase tumors.
This document provides guidelines for safety pharmacology and toxicology studies for pharmaceutical products. It outlines the objectives and types of studies recommended at different stages of clinical development, including safety pharmacology core battery studies, follow-up studies, reproductive and developmental toxicity studies, and human studies. Test systems, dose levels, durations, endpoints, and good laboratory practice standards are discussed for each type of nonclinical study.
A review on stages of drug development and alternative methods for animal stu...Frinto Francis
Various Stages of drug development, anaesthesia ,euthanasia, animals used for preclinical analysis, clinical trials, alternative methods for animal testing, blood withdrawal methods, ethical guidelines
The document provides information about toxicology and the Organisation for Economic Co-operation and Development (OECD) Guidelines for the Testing of Chemicals. It states that toxicology is the scientific study of adverse effects of chemicals on living organisms. It then discusses that the OECD guidelines are a collection of internationally agreed testing methods used by governments, industry and laboratories to identify potential hazards of chemicals. The guidelines cover various types of toxicity tests, including acute, sub-acute, sub-chronic and chronic toxicity tests, and are accepted globally as standard safety testing methods.
- Toxicology is the scientific study of adverse effects of chemicals on living organisms. It involves observing and reporting symptoms, mechanisms, detection and treatments of toxic substances in relation to human poisoning.
- The OECD promotes policies to improve economic and social well-being worldwide. It works with governments to understand drivers of change and sets international standards on issues like agriculture, tax, and chemical safety. India has cooperated with the OECD since 1995 through enhanced engagement programs.
- Toxicity testing involves various studies including acute, sub-acute, sub-chronic, chronic, and special toxicity (carcinogenicity) testing over different time periods. Chronic toxicity testing identifies target organs and characterizes dose-response relationships
This document discusses toxicity testing and provides details about various toxicity studies. It explains that toxicity testing involves observing adverse effects of chemicals in living organisms. It then describes different types of toxicity studies including acute, sub-acute, sub-chronic, chronic, and carcinogenicity studies. The document provides details about parameters evaluated in acute and chronic toxicity studies such as dosage, duration, symptoms observed, and endpoints. It also discusses alternative methods to traditional animal testing and guidelines for reporting toxicity study results.
GENERAL GUIDELINES FOR TOXICOPATHOLOGY STUDYRahul Kadam
The nonclinical safety study recommendations for the marketing approval
of a pharmaceutical usually include single and repeated dose toxicity
studies, reproduction toxicity studies, genotoxicity studies, local tolerance
studies, and for drugs that have special cause for concern or are intended
for a long duration of use, an assessment of carcinogenic potential. Other
nonclinical studies include pharmacology studies for safety assessment
(safety pharmacology) and pharmacokinetic (absorption, distribution,
metabolism, and excretion (ADME)) studies. These types of studies and
their relation to the conduct of human clinical trials are presented in this
guidance.
The document discusses various stages of drug development from preclinical to clinical trials in animals and humans. It describes studies conducted to determine toxicity, therapeutic index, adverse effects, and safety of new drug candidates. These include studies to evaluate single and repeated dose toxicity, reproductive toxicity, local toxicity, genotoxicity, and carcinogenicity. The goal is to accurately predict a drug's effects in humans based on animal studies and ensure safety before clinical trials.
Initial considerations for the study design include information on the test chemical's identity, properties, and results from previous toxicity tests. The guideline describes conducting a chronic toxicity study in rodents for 12 months, with the potential for interim kills and satellite groups. Key steps include dosing animals daily, observing them for signs of toxicity, and conducting clinical pathology, including hematology, clinical biochemistry, and urinalysis at various times. At the end, a full gross necropsy is performed and tissues are examined microscopically. Results are reported individually and summarized, including survival, body weights, food consumption, toxic responses, organ weights, and histopathological findings.
introduction to practical pharmacology, various experimental animal uses, CPCSEA guidelines, different phases of clinical trial, pre-clinical trial, important pharmacological definition
The identification of the carcinogenic properties of a chemical, resulting in an increased incidence of neoplasms, increased proportion of malignant neoplasms or a reduction in the time to appearance of neoplasms, compared with concurrent control groups.
The identification of target organ(s) of carcinogenicity.
The identification of the time to appearance of neoplasms.
Characterisation of the tumour dose-response relationship.
This document outlines the principles and types of non-clinical toxicity studies conducted in animals prior to testing pharmaceuticals in humans. It discusses general principles like complying with Good Laboratory Practice, using standardized equipment and protocols. It also describes the different types of toxicology studies including toxicokinetic, reproductive toxicity, teratogenicity and perinatal studies. The goal is to assess safety and predict potential adverse effects in humans by administering test substances to animals and observing toxicity.
This document provides an overview of acute appendicitis, including:
1. The anatomy of the appendix, which varies in length and position but has a constant base near the cecum.
2. The pathogenesis of appendicitis, which is usually caused by luminal obstruction leading to intraluminal distention and inflammation.
3. The clinical features of appendicitis, including initial periumbilical pain shifting to the right lower quadrant, anorexia, nausea, and tenderness at McBurney's point. Diagnosis can be difficult and is aided by clinical scoring systems.
Mr. J.A., a 64-year-old man, presented with progressive disorientation, fever, headaches, and neck stiffness. Examination found nuchal rigidity and a positive Brudzinski sign. His CSF was turbid with elevated proteins, low glucose, and high white blood cells. This suggested a diagnosis of tuberculous meningitis. Treatment began with daily isoniazid, rifampin, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for 7-10 more months. Dexamethasone was also prescribed for 6-8 weeks to reduce intracranial pressure and sequelae. The goals
General toxicology testing refers to a series of toxicity tests required by international regulators to prove safety in experimental animals prior to human testing. It includes acute, sub-acute, and chronic toxicity tests conducted according to OECD guidelines in rodents and non-rodents. Preclinical studies include phytochemistry, formulation development, pharmacology/pharmacokinetic profiling, safety toxicology studies, and efficacy studies. Toxicology studies are guided by regulatory requirements like OECD/ICH guidelines and Good Laboratory Practices to ensure quality. Acute, sub-acute, and chronic toxicity tests provide information on toxicity effects from single or repeated substance exposure over different time periods and help determine safe doses for clinical trials.
Toxicological Approach to Drug DiscoverySuhas Reddy C
This document outlines the toxicological approach to drug development. It discusses the importance of conducting various toxicity studies at different stages of drug development to ensure safety. These include single dose, repeated dose, fertility, reproductive, developmental and genotoxicity studies in animals. It describes the typical safety program involving staged approach and discusses factors to consider in designing toxicity studies. The goal is to obtain sufficient non-clinical safety data to support clinical trials and assess safety for human use.
Animal toxicity study requirements for conduct of clinical trial april 13 2019Akanksha William
This document provides guidance on conducting various types of animal toxicity studies required for clinical trials. It describes the objectives and key aspects of acute, repeated-dose, reproductive, and local toxicity studies. Acute toxicity studies in rodents aim to identify a safe starting dose for clinical studies. Repeated-dose studies in rodents and non-rodents over 14-180 days are used to identify target organ toxicity. Reproductive toxicity studies evaluate effects on fertility and development. Local toxicity studies assess hazards from dermal, ocular, or other routes of exposure. The document emphasizes standardized methods and selection of doses and species.
This document provides an overview of acute toxicity studies and OECD test guidelines for assessing acute oral toxicity. It discusses the principles and procedures for acute oral toxicity fixed dose tests per OECD Guideline 420. Key points include:
- Guideline 420 is an alternative to the conventional acute toxicity test that uses fewer animals and causes less suffering
- It involves dosing groups of animals with fixed doses (e.g. 5, 50, 300, 2000 mg/kg) and observing any signs of toxicity or mortality
- A sighting study is conducted to determine the starting dose for the main study
- Multiple animals are tested at each dose level in the main study with observation periods to monitor for any toxic effects
This document discusses various types of animal toxicity studies that are required before a drug can be administered to humans. It describes how these studies help establish the therapeutic index and predict adverse effects in humans. The key types of studies mentioned are systemic toxicity studies (including single dose, repeated dose, reproductive, and local toxicity), allergenicity/hypersensitivity studies, genotoxicity studies, and carcinogenicity/oncogenicity studies. Each type of study has specific objectives, test models used, parameters evaluated, and methods for conducting the studies and evaluating results. The studies aim to assess benefits and risks of drugs and establish their safety profiles before human use.
This document discusses various types of toxicology studies including acute, subacute, subchronic, and chronic toxicity studies. It provides definitions and describes the purpose and procedures for single dose acute toxicity testing of pharmaceuticals in animals. Classification criteria for substances based on exposure route and dose are presented. The document outlines observations, chronic toxicity studies, and principles of toxicity studies including following standard procedures and protecting animal welfare. Proposals for clinical studies include assessing drug exposure, plasma protein binding, metabolism, dose schedules, temporal relationships, and target engagement.
This document discusses principles of animal toxicology, including acute, subacute, and chronic toxicity testing. It defines key terms like toxicology, describes how drugs can cause toxicity, and explains different types of toxicity studies used to characterize a drug's safety profile. These include acute toxicity studies assessing effects of a single high dose, subacute studies examining impacts of repeat dosing over 14-28 days, and chronic studies evaluating long-term or lifetime exposure. The document also discusses LD50 values and how toxicology studies relate to pharmacology and clinical trials in the drug development process.
This document discusses the goals and requirements for preclinical safety and toxicity testing of new drug candidates. The primary goals are to estimate a safe starting dose for clinical trials, identify potential target organs of toxicity, and assess hazards that cannot be evaluated in clinical trials, like carcinogenicity. A variety of toxicity studies are required, including acute, repeated-dose, reproductive, and local toxicity studies. These studies must be conducted in two animal species, typically rats and non-rodents like dogs, and follow standardized guidelines for factors like number of animals, dose levels, routes of administration, duration and evaluation parameters. The results inform the design of subsequent clinical trials in humans.
This document discusses various types of animal toxicity studies conducted prior to clinical use of drugs in humans. It provides objectives and details of reproductive and developmental toxicity studies, local toxicity studies, carcinogenicity studies, and genotoxicity studies. Reproductive toxicity studies examine effects on fertility and development in offspring. Developmental toxicity studies evaluate effects during pregnancy and across lifespan. Local toxicity studies are required when drugs are administered via non-oral routes. Carcinogenicity studies identify substances that may induce or increase tumors.
This document provides guidelines for safety pharmacology and toxicology studies for pharmaceutical products. It outlines the objectives and types of studies recommended at different stages of clinical development, including safety pharmacology core battery studies, follow-up studies, reproductive and developmental toxicity studies, and human studies. Test systems, dose levels, durations, endpoints, and good laboratory practice standards are discussed for each type of nonclinical study.
A review on stages of drug development and alternative methods for animal stu...Frinto Francis
Various Stages of drug development, anaesthesia ,euthanasia, animals used for preclinical analysis, clinical trials, alternative methods for animal testing, blood withdrawal methods, ethical guidelines
The document provides information about toxicology and the Organisation for Economic Co-operation and Development (OECD) Guidelines for the Testing of Chemicals. It states that toxicology is the scientific study of adverse effects of chemicals on living organisms. It then discusses that the OECD guidelines are a collection of internationally agreed testing methods used by governments, industry and laboratories to identify potential hazards of chemicals. The guidelines cover various types of toxicity tests, including acute, sub-acute, sub-chronic and chronic toxicity tests, and are accepted globally as standard safety testing methods.
- Toxicology is the scientific study of adverse effects of chemicals on living organisms. It involves observing and reporting symptoms, mechanisms, detection and treatments of toxic substances in relation to human poisoning.
- The OECD promotes policies to improve economic and social well-being worldwide. It works with governments to understand drivers of change and sets international standards on issues like agriculture, tax, and chemical safety. India has cooperated with the OECD since 1995 through enhanced engagement programs.
- Toxicity testing involves various studies including acute, sub-acute, sub-chronic, chronic, and special toxicity (carcinogenicity) testing over different time periods. Chronic toxicity testing identifies target organs and characterizes dose-response relationships
This document discusses toxicity testing and provides details about various toxicity studies. It explains that toxicity testing involves observing adverse effects of chemicals in living organisms. It then describes different types of toxicity studies including acute, sub-acute, sub-chronic, chronic, and carcinogenicity studies. The document provides details about parameters evaluated in acute and chronic toxicity studies such as dosage, duration, symptoms observed, and endpoints. It also discusses alternative methods to traditional animal testing and guidelines for reporting toxicity study results.
GENERAL GUIDELINES FOR TOXICOPATHOLOGY STUDYRahul Kadam
The nonclinical safety study recommendations for the marketing approval
of a pharmaceutical usually include single and repeated dose toxicity
studies, reproduction toxicity studies, genotoxicity studies, local tolerance
studies, and for drugs that have special cause for concern or are intended
for a long duration of use, an assessment of carcinogenic potential. Other
nonclinical studies include pharmacology studies for safety assessment
(safety pharmacology) and pharmacokinetic (absorption, distribution,
metabolism, and excretion (ADME)) studies. These types of studies and
their relation to the conduct of human clinical trials are presented in this
guidance.
The document discusses various stages of drug development from preclinical to clinical trials in animals and humans. It describes studies conducted to determine toxicity, therapeutic index, adverse effects, and safety of new drug candidates. These include studies to evaluate single and repeated dose toxicity, reproductive toxicity, local toxicity, genotoxicity, and carcinogenicity. The goal is to accurately predict a drug's effects in humans based on animal studies and ensure safety before clinical trials.
Initial considerations for the study design include information on the test chemical's identity, properties, and results from previous toxicity tests. The guideline describes conducting a chronic toxicity study in rodents for 12 months, with the potential for interim kills and satellite groups. Key steps include dosing animals daily, observing them for signs of toxicity, and conducting clinical pathology, including hematology, clinical biochemistry, and urinalysis at various times. At the end, a full gross necropsy is performed and tissues are examined microscopically. Results are reported individually and summarized, including survival, body weights, food consumption, toxic responses, organ weights, and histopathological findings.
introduction to practical pharmacology, various experimental animal uses, CPCSEA guidelines, different phases of clinical trial, pre-clinical trial, important pharmacological definition
The identification of the carcinogenic properties of a chemical, resulting in an increased incidence of neoplasms, increased proportion of malignant neoplasms or a reduction in the time to appearance of neoplasms, compared with concurrent control groups.
The identification of target organ(s) of carcinogenicity.
The identification of the time to appearance of neoplasms.
Characterisation of the tumour dose-response relationship.
This document outlines the principles and types of non-clinical toxicity studies conducted in animals prior to testing pharmaceuticals in humans. It discusses general principles like complying with Good Laboratory Practice, using standardized equipment and protocols. It also describes the different types of toxicology studies including toxicokinetic, reproductive toxicity, teratogenicity and perinatal studies. The goal is to assess safety and predict potential adverse effects in humans by administering test substances to animals and observing toxicity.
This document provides an overview of acute appendicitis, including:
1. The anatomy of the appendix, which varies in length and position but has a constant base near the cecum.
2. The pathogenesis of appendicitis, which is usually caused by luminal obstruction leading to intraluminal distention and inflammation.
3. The clinical features of appendicitis, including initial periumbilical pain shifting to the right lower quadrant, anorexia, nausea, and tenderness at McBurney's point. Diagnosis can be difficult and is aided by clinical scoring systems.
Mr. J.A., a 64-year-old man, presented with progressive disorientation, fever, headaches, and neck stiffness. Examination found nuchal rigidity and a positive Brudzinski sign. His CSF was turbid with elevated proteins, low glucose, and high white blood cells. This suggested a diagnosis of tuberculous meningitis. Treatment began with daily isoniazid, rifampin, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for 7-10 more months. Dexamethasone was also prescribed for 6-8 weeks to reduce intracranial pressure and sequelae. The goals
This document provides guidelines for the proper storage of pharmaceuticals. It discusses shelf life and expiration dates, first-in first-out (FIFO) inventory management, general storage conditions, temperature requirements, security, and visual inspections. Key recommendations include storing products by expiration date with earliest dates in front, maintaining proper temperature controls, limiting access to secure items, and regularly inspecting products for quality issues.
This document discusses fungal infections caused by dermatophytes, specifically various types of ringworm. It describes the etiological agents that cause ringworm, how they infect keratinized tissues like skin, hair, and nails. It then covers the clinical manifestations and treatment for different types of ringworm infections based on the infected location, such as tinea pedis (athlete's foot), tinea corporis (body ringworm), tinea cruris (jock itch), and tinea unguium (nail infection). Topical and oral antifungal treatments are outlined depending on the severity of the infection.
This case presentation summarizes a 22-year-old male patient who presented with abdominal pain and was found to have gangrenous appendicitis. He underwent an appendectomy and was on post-operative day 4. His vital signs were stable. On examination, his surgical incision was clean with no signs of infection. Laboratory tests showed elevated white blood cell count. He was being treated with ceftriaxone, tramadol, and diclofenac. The pharmacist recommends adding metronidazole to help treat any anaerobic infections and outlines a care plan to prevent surgical site infections and monitor the patient's recovery.
Shock is a life-threatening condition where the circulatory system fails to deliver oxygen to tissues. It can progress rapidly to organ failure and death if not corrected. Shock is generally classified as hypovolemic, cardiogenic, or distributive. Treatment involves identifying the cause, restoring blood volume through fluids, providing oxygen support, treating infection if present, and using vasoactive drugs or inotropes. The goals are to restore tissue perfusion and prevent complications like multiple organ failure. Early diagnosis and management of shock is crucial to prevent permanent damage or death.
CHAPTER ONE & TWO LOGIC AND PHILOSOPHY.pptxBarentuShemsu
This document provides an introduction to philosophy by outlining some of its key concepts and fields. It begins by defining philosophy as the love of wisdom and noting that philosophy deals primarily with fundamental issues rather than having a single subject matter. The document then outlines some of philosophy's major fields, including metaphysics, epistemology, axiology, and logic. For each field, it provides brief definitions and examples of the types of questions addressed. The document emphasizes that philosophy is an activity that encourages critical examination and reflection on life and reality.
1. HIV/AIDS remains a major global public health issue, with sub-Saharan Africa disproportionately affected.
2. HIV targets CD4 cells and progressively destroys the immune system, leaving the body vulnerable to opportunistic infections.
3. The virus has several stages in its lifecycle within the human body, allowing it to evade detection and establish chronic, long-term infection.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Does Over-Masturbation Contribute to Chronic Prostatitis.pptxwalterHu5
In some case, your chronic prostatitis may be related to over-masturbation. Generally, natural medicine Diuretic and Anti-inflammatory Pill can help mee get a cure.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
2. Learning Objectives
Discuss the studies on general toxicity
Describe developmental & reproductive toxicity
studies
Explain the different methods of mutagenicity
studies
Describe the tests used to study carcinogenic
effect of chemicals
2
3. Chapter Outline
Studies on general toxicity:
Acute, sub-acute, sub-chronic & chronic toxicity
studies
Studies on various types of specific adverse
effects:
Developmental & reproductive toxicity
Mutagenicity
Tests for carcinogens
Immunotoxicity assessment
Irritation & sensitization - local tolerance studies
3
4. I. Studies on General Toxicity
Toxicological testing is best performed with pure
substances since examination with chemical
mixtures is practically impossible & may give rise to
erroneous conclusions due to possible chemical
interactions
If it is necessary to determine the toxicity of a cpx
mixture, investigation should start by establishing
the composition of the mixture & determining which
components of the mixture are bioactive
4
Principles of descriptive animal toxicity
tests
Two main principles underlie all descriptive animal
toxicity testing
A. The effects produced by a compound in lab
animals, when properly qualified, are
applicable to humans
• On the basis of dose per unit of body surface,
toxic effects in humans are usually in the same
range as those in experimental animals
• On a body weight basis, humans are generally
more vulnerable than are experimental animals
1
5. Studies on General Toxicity…
Each substance then must be classified &
characterized with respect to its physicochemical
properties
The stability of a given substance determines how it
should be administered for testing, particularly if it is
inactivated in the GIT
In general, the starting point for toxicological testing
of new substances is testing in lab animals
A chemical may be administrated to animals by oral,
dermal, IV, IM or IP routes
5
6. Studies on General Toxicity…
The ideal experimental animal is one that
metabolizes & secretes a substance in the same
manner as humans do
Thus, rodents, hamsters, rabbits, cats & dogs are
the most frequent human surrogates used for
toxicological testing
Mainly b/c they are economical, amenable to
frequent handling & lacking in the vomiting reflex
Other animals, such as monkeys, are also used
6
7. Studies on General Toxicity…
Metabolic differences b/n humans & surrogate test
animals can result in erroneous conclusions about
the activity of a substance in humans
Use of younger animals provides the advantage of
obtaining faster results due to their higher rate of
metabolism, as well as their being cheaper to
purchase & house
Age & gender of animals can influence the
outcome of the investigation
7
8. Studies on General Toxicity…
The purity of the substance is very important,
since impurities may significantly influence
toxicological findings
Before animal testing is started, a literature search
must be done to collect available results of any
previous testing
If the test substance is administrated to
experimental animal by mixing it with food or water,
it may be affected by oxidation (i.e., through contact
with air), or by temperature variations or by the
feeding habits of the experimental animals
8
9. Studies on General Toxicity…
Gastric intubation (gavage), an artificial means of
substance introduction, has advantages with respect
to dosing exactness & reduced variation
The gavage is performed after the animals have
fasted in order to avoid mixing chemical test
substances with stomach contents
In general, the chemical dose should not exceed
5% of the test animal’s diet
9
10. Studies on General Toxicity…
Alternative test methods:
The use of lab-cultured single-cell organisms
Isolated organs or mammalian cell lines
NB: The advantage of animal testing:
The possibility to examine the results of
different routes of exposure under controlled
conditions
10
11. Studies on General Toxicity…
However, differences in genetic pool, lifespan,
susceptibility, metabolic pathways & other
parameters of organic life, present serious
limitations when extrapolating the results of
animal testing to human populations
Animal experiments are usually classified
according to their duration as:
Acute, sub-acute, chronic or sub-chronic testing
Chronic & acute toxic effects for a specific toxicant
can differ both qualitatively & quantitatively
11
13. A. Acute toxicity studies
Objectives:
To determine the Median Lethal Dose (LD50) after a
single dose administered through one or more
routes, one of which is the intended route of
administration in humans
To determine Maximum Tolerated Dose (MTD) & No
Observable Effect Level (NOEL)
To identify potential target organs for toxicity,
determine reversibility of toxicity, & identify
parameters for clinical monitoring
To help select doses for repeated-dose toxicity tests
13
14. Acute toxicity studies…
Duration:
A few days to 2 wks after a single dose
Test system/animal system:
2 species required: mice, rats, or rabbits or dogs
Dose administration:
Oral (by gavage or with food), SC, IP, Intradermal,
Inhalation, Intranasal, Topical (epicutaneous), IV
Parameters:
Mortality, clinical pathology, gross necropsy, weight
change, signs of toxicity
14
15. B. Sub-acute toxicity studies
Objectives:
To determine toxicity after repeated
administration of the test material
To help establish doses for subchronic studies
Duration: 14 days
Test system/animal system
2 species required: mice, rats, rabbits, guinea
pigs, dogs
15
16. Sub-acutetoxicity studies…
Dose administration:
3 to 4 doses given by the same routes as
previous toxicity tests
Parameters:
Mortality
Signs of toxicity
Pathology & histopathology
Weight change
Clinical pathology
16
17. C. Sub-chronic toxicity testing
Objectives:
To establish a “no observable effect level"
(NOEL)
To characterize D-R r/ships following repeated
doses
To further identify & characterize specific organs
affected after repeated administration
To predict a reasonable & appropriate dose for
chronic exposure studies (MTD)
17
18. Sub-chronic toxicity testing…
Duration:
Commonly 90 days, but varies from 2 wks to 6
months or up to 10% of species’ lifespan
Test system/animal system:
2 species required: rodents, dogs
Dose administration:
At least 3 doses given by the same routes as
previous toxicity tests; the lowest producing no
apparent toxicity & the highest producing toxicity
but less than or equal to 10% mortality
18
20. D. Chronic toxicity testing
Objectives:
To evaluate the cumulative toxicity of chemicals
To assess carcinogenic potential
Duration:
Rodents - 6 to 24 months; non-rodents - 12
months or longer or up to 10% of species’
lifespan
Length depends on intended period of human
exposure
20
Chronic toxicity studies
Long-term or chronic exposure studies are
performed similarly to subchronic studies except
that the period of exposure is longer than 3 months
In rodents, chronic exposures are usually for 6
months to 2 years
Chronic studies in non-rodent species are usually
for 1 year but may be longer
The length of exposure is somewhat dependent on
the intended period of exposure in humans
21. Chronic toxicity testing…
Test system/animal system:
2 species required: Rodents, dogs
Dose administration:
As in sub-acute/ subchronic toxicity studies
Parameters:
Mortality
Pathology & histopathology
Weight change
Clinical pathology of all animals (mortalities &
survivors)
21
22. II. Studies on various types of
specific adverse effects
Studies on various types of specific adverse
effects
Developmental & reproductive toxicity
Mutagenicity
Tests for carcinogens
Immuno-toxicity assessment
Irritation & sensitization - local tolerance
studies
22
23. A. Developmental & reproductive
toxicity
Developmental toxicology:
The study of adverse effects on the developing
organism occurring anytime during the life
span of the organism that may result from
exposure to chemical or physical agents
• Before conception (either parent)
• During prenatal development, or
• Postnatally until the time of puberty
23
24. Developmental & reproductive
toxicity…
Teratology:
The study of defects induced during
development b/n conception & birth
Reproductive toxicology:
The study of the occurrence of adverse effects
on the male or female reproductive system
that may result from exposure to chemical or
physical agents
24
25. Developmental & reproductive
toxicity…
a) General fertility & reproductive performance
(segment I) studies:
They are usually performed in rats with 2 or 3
doses (20 rats per sex per dose) of the test
chemical (neither produces maternal toxicity)
Males are given the chemical 60 days & females
14 days before mating
The animals are given the chemical throughout
gestation & lactation
25
26. Developmental & reproductive
toxicity…
Segment I studies…
Typical observations made include:
• The % of females that become pregnant
• The number of stillborn & live offspring,
• The wt, growth, survival, & general condition of
the offspring during the first 3 wks of life
26
27. Developmental & reproductive
toxicity…
b) Teratogenic effects (segment II) studies:
Teratogens are most effective when administered
during the 1st trimester, the period of organogenesis
Thus, the animals (usually 12 rabbits & 24 rats or
mice per group) are usually exposed to one of three
dosages during organogenesis (day 7 to 17 in
rodents & days 7 to 19 in rabbits), & the fetuses are
removed by cesarean section a day before the
estimated time of delivery (gestational days 29 for
rabbit, 20 for rat, & 18 for mouse)
27
28. Developmental & reproductive
toxicity…
Segment II studies..
The uterus is excised & weighed & then
examined for the number of live, dead, &
resorbed fetuses
Live fetuses are weighed
Half of each litter is examined for skeletal
abnormalities & the remaining half for soft tissue
anomalies
28
29. Developmental & reproductive
toxicity…
c) Perinatal & postnatal toxicities of chemicals
(segment III) studies:
This test is performed by administering the
test compound to rats from the 15th day of
gestation throughout delivery & lactation
Then determining its effect on the birth-
weight, survival, & growth of the offspring
during the first 3 wks of life
29
30. B. Mutagenicity
Mutagenesis is the ability of chemicals to cause
changes in the genetic material in the nucleus of cells
in ways that allow the changes to be transmitted
during cell division
Mutations can occur in either of 2 cell types, with
substantially different consequences
Germinal mutations
Somatic mutations
30
31. Mutagenicity…
Germinal mutations:
Damage DNA in sperm & ova, which can
undergo meiotic division & therefore have the
potential for transmission of the mutations
to future generations
If mutations are present at the time of
fertilization in either the egg or the sperm, the
resulting combination of genetic material may
not be viable, & the death may occur in the
early stages of embryonic cell division
31
32. Mutagenicity…
Germinal mutations…
Alternatively, the mutation in the genetic
material may not affect early
embryogenesis but may result in the death
of the fetus at a later developmental period,
resulting in abortion
Congenital abnormalities may also result
from mutations
32
33. Mutagenicity…
Somatic mutations:
Mutations in all other cell types & are not
heritable but may result in cell death or
transmission of a genetic defect to other cells
in the same tissue through mitotic division
33
34. Mutagenicity…
B/c the initiating event of chemical
carcinogenesis is thought to be a mutagenic one,
mutagenic tests are often used to screen for
potential carcinogens
Numerous in vivo & in vitro procedures have
been devised to test chemicals for their ability to
cause mutations
34
35. Mutagenicity…
Some genetic alterations are visible with the light
microscope
In this case, cytogenetic analysis of bone
marrow smears is used after the animals have
been exposed to the test agent
B/c some mutations are incompatible with normal
development, the mutagenic potential of a
chemical can also be evaluated by the dominant
lethal test
This test is usually performed in rodents
35
36. Mutagenicity…
The dominant lethal test…
The male is exposed to a single dose of the
test compound & then is mated with two
untreated females weekly for 8 wks
The females are killed before term, & the
number of live embryos & the number of
corpora lutea are determined
36
37. Mutagenicity…
Salmonella/microsome/Ames test:
The test for mutagens that has received the
widest attention that is developed by Ames &
colleagues
This test uses several mutant strains of S.
typhimurium that lack the enzyme
phosphoribosyl ATP synthetase, which is
required for histidine synthesis
These strains are unable to grow in a histidine-
deficient medium unless a reverse or back-
mutation to the wild type has occurred
37
38. Mutagenicity…
Ames test…
Other mutations in these bacteria have been
introduced to enhance the sensitivity of the
strains to mutagenesis
The 2 most significant additional mutations
enhance penetration of substances into the
bacteria & decrease the ability of the bacteria
to repair DNA damage
38
39. Mutagenicity…
Ames test…
B/c many chemicals are not mutagenic or
carcinogenic unless they are biotransformed to
a toxic product by enzymes in the ER, rat liver
microsomes are usually added to the medium
containing the mutant strain & the test chemical
The number of reverse mutations is then
quantified by the number of bacterial colonies
that grow in a histidine-deficient medium
39
40. C. Tests for carcinogens
a) The Standard Test:
The currently accepted design for
carcinogenicity testing is to expose rats & mice
to the agent for about 2 years
For each species, 50 male & 50 female animals
per group are dosed with a vehicle or the test
agent in that vehicle
Daily observations are made & if any animals
become moribund during the experiment, they
are killed so that tissues are not lost due to
autolysis
40
41. Tests for carcinogens…
The Standard Test..
All animals, including those that survive to
the scheduled end of the experiment, are
subjected to autopsy & almost 40 different
tissues are taken from each animal for
histological examination
All observations are recorded, summarized &
analyzed
41
42. D. Immunotoxicity Assessment
Objective:
To determine the potential of a test material to
induce immune suppression or immune
enhancement
Duration:
Subacute (14 days) or sub-chronic (90 days)
exposure
Test system/animal system: Rodents
Dose administration:
Repeated doses administered as in sub-
acute/sub-chronic toxicity studies
42
43. Immunotoxicity Assessment…
Parameters:
Level 1:
• Hematology
• Histopathology or lymphoid organs
• Quantity of T- & B-cells (cellularity of lymphoid
organs)
• Blastogenesis (mitogen responsiveness; mixed
lymphocyte reaction)
• Quantitation and funciton of natural killer cells
• Macrophage function
• Cytokine production
43
44. Immunotoxicity Assessment…
Parameters…
Level 2:
• Kinetics of antibody production to T-
dependent antigens
• Quantity of IgM/IgG-producing (plaque-
forming) cells
• Delayed hypersensitivity responses to known
sensitizers
• Immune response to infectious agents (e.g.,
Listeria, Streptococcus)
• Immune response to transplantable tumors
44
45. E. Irritation & sensitization - local
tolerance studies
Objectives:
To determine the potential of a test material to
provoke ocular irritation, dermal irritation, or
sensitization
Duration:
Irritation - 1 hr to 3 wks after a single topical or
corneal administration
Sensitization - intradermal or topical induction
doses followed by topical challenges with a non-
irritating dose (6 - 8 wks total)
Test system/animal system: Rodents, rabbits
45
46. Irritation & sensitization - local
tolerance studies…
Test system/animal system: Rodents, rabbits
Dose administration
Single patch administration
Multiple doses over 2—4 weeks
Topical (epicutaneous), intradermal, or corneal
46
47. Irritation & sensitization - local
tolerance studies…
Parameters:
Degree of pruritis, erythema, edema, papules,
and vesicles
Corneal irritation, swelling, or injury
Microscopic integrity of corneal endothelium
Other features of the eye (conjuctive, cornea,
iris, lens, anterior portion of vitreous humor)
47