TOXICOLOGY

A Note On…. “Classes on Toxicology”

It is planned to bring you a” Class on Toxicology”, every Friday. Today 28/09/2018, the Topic will be An Introduction to Toxicology. What is Toxicology and the general concept about Toxicology is explained. Dr. Fernandez, a professional Toxicologist is preparing the content of the Classes and available for your queries and suggestions through the Comments column. You are welcome to the classes.

These classes are meant for the general public, as a tool to get educated about our daily life in this Earth and understand how we are encircled by bad Air, contaminated Water and spoiled Soil. The Hon. Ministers, respected Citizens, Government servants, technical and administrative people in the Medical and Veterinary areas, persons working in any Industry, Agriculture and Fisheries, transports, Parents of normal as well as Special children, all will be benefitted by these classes. Toxicology will help in tackling the use of various commodities that we use daily or environments to which we are exposed.

Why this classes? And free?

 I completed my studies and believe that public funds had been spent on me and my education. I earned a Doctorate from Kerala University. I was nominated to present before the Expert Committee assessing the University for Accreditation. “ I am a product of this University and I am happy to state that the way university curriculums are prepared and taught gave me needed exposure to master any  strange topic and to be confident in executing any assigned jobs, to the satisfaction of the Superior.

Therefore, I feel that I am indebted to the Public to share my knowledge, with them. My decision to do so, is the result of bringing me up. My father Dr. Alfred Cyril Fernandez, a native of Quilon, was a product of Culcutta Veterinary College and he was the first Veterinary Surgeon of Corporation of Trivandrum. My Mother Mrs. Mariam, a native of Kottayam was my teacher, mender of my quality and made me always stay in the path of truth and truth only and be helpful to everybody to the extend possible, which made me a person acceptable to the majority and a patient listener. In case you miss a class from me on a Friday, just forgive me, it must be due to some personal reason.

My mobile no is 9447777985 and- mail ID is acfernandez04@yahoo.com.

An Introduction                                                                                                         

Toxicology is commonly known as the study of poisons. The subject has been understood and explained in common terms from olden times. Toxicology was noted and in practice from the B.C era. It was connected with plant foods and agriculture products of different time eras. Some plants were found to be toxic or lethal to animals as well as to humans. Humans soon learned that these toxic materials could be used to the advantage to dissuade or eliminate predators or even fellow humans for various reasons. As time passed man learned that poisons are lethal but it depended on the strength and dose of the poison in question. He also understood that some poisons have medicinal properties at lower dose levels and useful for humans and animals. Some poisons were found useful to keep the pests away from the valuable agriculture plants as well as for safe storage of the plant products. As time passed it was found that poisons were also seen in animals. Modern times and industrial developments and the great world wars exposed the poisonous nature of metals, non metals, minerals, many manmade materials, radiation etc. Presently, Toxicology has become an interdisciplinary subject practiced in participation by Biologists, Biochemists, Chemists and Physicists. Further many other specialists like, Ecologist, Environmentalists, Drug designers, Cosmetic designers, Biomedical Device designers, Heavy Industrialists, Various transport designers including Space farers and Designers of Closed environments come into the realm of Toxicology as Man is the consumer of their products or the persons who has to endure the Toxic effects of their end products or bye products.

History Of  Toxicology

Tracing back Toxicology, is really a retreat through olden literature in Chinese, Greek, Vedas, Persian, French, British etc. Chinese Medicine records that Shen Nung (2696 B C ) tasted 365 herbs and authored a Treaties “Herbal Medical Experiment on poisons.” Homer describes the use of Poisoned arrows in his epics “The Odyssey and Iliad” in 860 B C. Here he enlightens on Tokkicon or poisoned arrows used very commonly on wars conducted during his life period and the root of the word, Toxicology. Hippocrates (400 B C ) in his writings showed that toxins or poisons exerted their effects by getting absorbed into the living system and this could be treated by preventing absorption by various means. In the Treaties “ De Historia Plantarum, 370 B C”, Theophrastus describes numerous Poisonous plants. Nicander of Colophon 185 B. C., physician to King Attalus of Bythnia studied use of poisons, its effects, symptoms of poisoning and the effects of anti dots and nature of recovery or death on prisoners, with King’s permission. The use of linseed for inducing vomiting and sucking of poison from the wounds made by venomous animals are his suggestions as part of treatment. Lucius Cornelius Sulla of Roman empire enacted the first law against poisoning in 82 BC to protect against careless dispensing. The Greek physician Discorides ( 40 -90 AD ) travelled a lot, mostly along with the Greek Army and wrote about plants that have medicinal value as well as that were poisonous. He classified poisons as originating from Plants, animals and minerals. He is the one to suggest emetics as a means of treating poisonous cases especially if the route of poisoning is oral. Ibn Wahshya  (860 -930 ), an Arab Botanist and thinker wrote a book on poisons. Moses Maimonides(1135- 1204 A. D. ) , a Jewish Philosopher and physician wrote about Poisons and their Treatments and criticized some of the methods of treatments of Poisoning, practiced earlier. His writings are considered as earlier notes on the Topic toxicology. Matheu Joseph Benavanthura Orfila  (1787 – 1853) a Spanish Scientist, known as the founder of Modern toxicology, as well as that of forensic toxicology. His book “ Treaties on Poisons” was a breakthrough  Moses Maimonides(1135- 1204 A. D. ) , a Jewish Philosopher and physician wrote about Poisons and their Treatments and criticized some of the methods of treatments of Poisoning, practiced earlier. His writings are considered as earlier notes on the Modern toxicology. Use of poisons in eliminating enemies saw a growth during this period. The beginning of 1900 saw the development of Chemistry in relation to Biology and the idea of mechanisms of action came to the fore. Rudolph Peters of Netherland, studied Arsenic gases used in the wars and came out with Anti Lewisite as an antidote for the exposure. From there on the Development of Science was very fast and embraced almost every aspect of life on earth. Man faced a situation where he has to find out ways to detoxify the Air, Water and the Soil he has to survive. His activities has contaminated even the Space and the two Arctic regions. So the modern world has the most modern techniques to assess the toxicity of any materials and to design a way to use them safely, with out which Human race could not survive for long, to write and read about Toxicity and Toxicology. 

09/11/2018

Classification of Toxicology

Analytical Toxicology, Applied Toxicology, Clinical Toxicology, Veterinary Toxicology, Forensic Toxicology, Industrial Toxicology, Environmental Toxicology are considered to be major divisions of Toxicology, in general. Toxicology as we know encompass the study of poisons, in the early years. At present, Toxicology touches any materials and it’s safety and it’s nature of hazard or risk in use or exposure. Thus Toxicology has become a broader Topic applied to various areas and subjects. When you want to study the hazards from food, it becomes food toxicology. You will observe that, to study food toxicology, the toxicologist has to have a team of experts to analyze the chemical composition, contamination if any, in the food before and after preparation, safety of packing material, bacterial contamination and sterility of the packed or served food. Likewise, drugs, cosmetics, dress materials, cleaning materials, insect repellants, construction materials of the Residence etc. needs to be safe for prescribed use and toxicology plays an important role in the day today life. Therefore, the general classification put up here is not a rigid one and could be added or changed. Academic toxicology, Regulatory toxicology, Occupational toxicology, Immune toxicology, Genetic toxicology, Contract toxicology, Political Toxicology etc. are some examples that we will come across. Toxicologist needs to understand the cause of toxicity and the extend of the damage brought about by the causative agent. For that he has to analyze the tissue samples, organ samples, blood, urine etc. and the causative material if any left. Spectroscopy, Chromatography and Immunological assays are used to detect, identify and measure the toxic material in question during a Toxicological study. Toxicologist has to evaluate the nature and mechanism of action of a poison or a material in biological systems, he applies various techniques available in Biochemistry, Pharmaco dynamics, Pharmacokinetics, Instrumental chemistry, Medicinal Chemistry etc. This area is denoted as Applied toxicology. When cases come up with over dose of medication, substance of abuse or poisoning, exposure to chemical burns or radiation in an Emergency Medicine Centre, the Clinician with special training in the management of such cases, evaluates each case, asses the extend of hazardous exposure and prescribe medical care for the patients. This area of Medical practice, where science of toxicology is employed in the treatment of patients is known as Clinical Toxicology. Like wise, the science of Toxicology used in conjunction with Veterinary Medicine is known as Veterinary toxicology. Other than the routine diagnosis and  treatment animals, the study of contaminants entering human food through animals, ecological and environmental contamination of animal habitat and foods, accidental poisoning from plants and venomous animals etc. also are relevant under this topic. Use of science of Toxicology in investigating the cause of poisoning, death by poisoning, identifying the nature, quantity and time of poisoning, misuse of drugs and chemicals falls under Forensic toxicology. Industry is an important word in modern world. Whatever we use in our daily life is produced in an industry. Any material or any product comes out of chemicals, physical forces, temperature and through lot of mechanization. In the manufacturing process, in transportation of raw materials and finished products the environment of production, packing, transport are polluted by the raw materials, accessories used to aid production process, packing, labeling etc. The work force and the people staying near and around the industry are sure to get a share of contamination. It may be through Air, Water or the soil where the waste material from the industry is dumped. This result in the deterioration of health of the industry worker as well as the people, animals and plants in the locality where the industry is situated. Such situations has initiated the subject Industrial Toxicology. The occurrence of contaminated Air, Water and Soil is very common in any places on the Earth, even the Arctic regions and the Space. As we are aware, the environment is contaminated and the branch of toxicology concerned with the health of Human beings, animals, plants and all living beings is, Environmental toxicology. Science of toxicology, assures safety and lead us to capably use anything that is hazardous to our advantage by designing safe protocols for use.

20/11/2018

Classes on toxicology:- Xenobiotics
Toxicology is all about materials or chemicals that are not normally found in an organism, a Xenobiotic. Living organisms will make reactions or responses towards the xenobiotics that enter the living organism. What is the xenobiotic in Question, the quantity that entered the body, the number of times the xenobiotic entered, the route of entry, the residue that is left in the organism etc. are questions which a Toxicologist ask and try his best to find out. Without these information he will not be able to access the true nature of the hazard and help to ameliorate the condition of the living organism. The xenobiotics that are usually hazardous are commonly known as poisons. In case the xenobiotic in question is a known material or poison, the toxicologist may get readily available information on the chemical nature, safe dose, possible responses of the living body towards the substance, degeneration within the body etc. and may be able to suggest methods to neutralize or detoxify the effects. The xenobiotics can enter the body from the environment or ingested knowingly or purposefully. The Air, Water and the Soil in the environment contain lot of xenobiotics, that will enter the living organism through inhalation, ingestion, absorption by skin. The same routes are used intentionally to consume poisons or administer poisons or substance of abuse.
23/11/18.

Classes on Toxicology:- Dose

 “Dose” simply means to the common man, the quantity of a medicine or drug prescribed by the Physician to be taken at a time. When we have fever, the doctor prescribes fever medicines. It is 500 mg of antipyretic for an adult, 3 times in a day, usually at 8 hr intervals, may be for 3 days or as advised by the Physician. Like this we know about the prescribed medicines for treating various illness have doses to follow. But in the case of Xenobiotics, when we are exposed, that can be a single dose as in the case of radiation or corrosive gases like chlorine or carbon monoxide, cosmetic cream applied to the skin. Here the dose is single exposure, but quantity of the xenobiotic is unknown and the effect of that exposure depends on the nature of the xenobiotic, period of exposure, the health of the exposed etc. How much xenobiotic was present?, the toxicologist has to estimate after studying the source, nature and period of exposure and clinical lab data from the exposed.

In the case of a drug or a xenobiotic the intake at a time could be “a dose”. The frequency at which the dose is repeated and the duration for which the dose is repeated is important and gives an idea of “total dose”. But when we take into consideration the response of the living system to eliminate the drug or xenobiotic, the quantity that is left in the body after elimination becomes the “internal dose”. The biological process involved in the elimination of Dose that is administered imposes problems in estimating the internal dose. “External dose” is another term denoting the dose equivalent received from radiation sources outside the body or living organism. Another common term used is “Threshhold dose” which means the lowest amount or exposure level of a toxic substance at which a specified and measurable effect manifests. I hope, the reading on “Dose” will give an idea about the different terms used in Toxicology. When we are dealing with response, mechanisms, biochemistry, testing etc. in Toxicology, we will come across more terms related to toxicology, pharmacology and medicine and will elaborate on them.

30/11/2018

Classes in Toxicology:-  Exposure

Exposure to a xenobiotic present in Air, Water or soil can happen through skin by dermal absorption, by inhalation through the respiratory system or by ingestion through the digestive tract. The same is true for drugs. Further xenobiotics can enter the body via food, drugs that are consumed as routine in daily life or administered intentionally by self or a third person. These are called route of exposure. Oral, inhalation and dermal are the common routes. Substances can enter the body through the Parenteral route too, ie. the entry of xenobiotics through intramuscular, intra dermal, subcutaneous, intravenous or artery. Food, medicines, water are the common materials we ingest and contamination through these vehicles is possible. Through inhalation we breath in air and any contaminants that is very common in the immediate environment surrounding us. Dermal absorption is common from the water we use, cosmetics, soaps and detergents, skin drugs or work related materials. Parenteral route commonly involved with prescribed medicines drugs of abuse or given by illegal means / options. Patterns of Exposure are important to be kept in mind. It can be one time, acute exposure or continuous, chronic exposure. This may be also a high dose acute exposure or a low dose chronic exposure.

When we talk about exposure we have to consider dose, age, body size and time also. Already we have noted basics about dose. An adult may need 650 mg (thrice a day) of antipyretic drug to control fever but  for a child 650 mg is toxic. Child may need only may be less than 80 mg. Another parameter is that 100 mg of “X” substance will lead to death of an adult as a single dose, it need not lead to death if taken 10 mg per day over a period of 10 days. Commonly the dose is set by mg per kilogram body weight per day or, mg/liter for liquids and, mg/m3 for air and other units like parts per million, parts per billion and parts per trillion are  well in use.

 But when doses are compared with different species of animals it may be by body surface area. The unit of time during which a dose is administered is accepted is “a or one day”. When xenobiotics in question are strong poisons the dosage will be lesser that mg/kg, namely microgram, nanogram, picogram etc.

When we talk about exposure we have to know about the response also. What is the response of an organism to an acute or chronic exposure to a Xenobiotic, which will be another day’s topic.

11/12/18

Classes on Toxicology:-Response

We respond to friendly calls and conversations. Our response to fire is to douse it and call for help if required. In toxicology, response is the action or reaction of the organism towards exposure to a xenobiotic. We have seen that exposure can be through inhalation, ingestion, through skin etc. This response depends on the dose to which the organism was exposed. This reminds use of the basic principle in toxicology that the dose decides the response, whether a material is Toxic or nontoxic. The living organism could be exposed to various chemical, radiological, so called inert materials through the environment in which they exist. These exposures bring about responses according to the concentration of these xenobiotic, finding a way into the organism. Take the case of burning of waste in the open. There is heat and smoke. The nature of heat and smoke varies with the content of the waste. Our response is to avoid the smoke, as it gives a burning sensation to the eyes and suffocating to the lungs. These are immediate response. In reality the acidic nature of the smoke makes it dissolve in the tears and form acid which gives irritation to the eyes and make it appear red in color and swollen. The same effect is happening with in the lungs and the cells in the lung gets swollen and suffocation happens. Here the response is from the tissue and as time pass, the acidic portion is scavenged by the body and relief is obtained. So the initial response of the body gradually may fade if the nature of exposure is acute or temporary. If the exposure is going to be continuous or the concentration of the exposure is going up, then the response will become severe and the organism continues to be in the smoky environment, the response becomes more suffocation because of lung tissue, failure to supply oxygen to the whole body, resulting in a stand still of body functions and death. The response depends on the status of the environmental conditions and availability of emergency medical assistance. To understand and asses the response of living organism to toxic materials, various methods have been developed and in place. When we move ahead, we will look into these facts, where we will come across lot of scientific terms in relation to dose, exposure and response.

14/12/2018

Classes on Toxicology:- Dose and Response

From the previous readings we understood the basics of Dose and Response separately. Today we will try to understand how they relate to each other in a toxicological study setting. Dose, response relationship is described based on studies conducted on experimental animals, clinical trials in human beings and cell culture studies. When a population is exposed to a toxicant or poison the response may vary from person to person or to say there may be a group that is affected severely and another group affected in general. That indicates there could be variation in response at a particular dose. But in general you can observe an increase in response as the dose increase and reaches a stage where all exposed are severely affected or dead. The final dose which brings in death is known as the lethal dose. The lowest dose at which an observed response is evident is known as threshold dose. If you are plotting the response to a xenobiotic or a poison in a standard graph, the X axis for dose and Y axis for response, the point at which the response is noted becomes the threshold dose level and as the dose increases the curve also increases and the point at which the response is 100% severely affected or mortality. The threshold level will vary for each substance and the potency increases as the slope becomes greater. The quantity of xenobiotic or to a poison to which an individual or organism is exposed or administered over a period of time or in several and individual doses may be considered as administered dose, the dose at which the individual or organism responds initially is called the threshold dose, the division of the total dose and its administration at different period of time decreases the toxic effect. All these factors are necessary for determining dose response relationship. As we have noted earlier, the common dosage unit is mg per Kilogram body weight per day. As we read on we will come back to the basics of dose and response and their relationship to acute and chronic exposures and responses.

21/12/2018

Classes on toxicology:- Acute Exposure

We now know what is meant by Exposure in the toxicology field. Daily we are exposed to hundred and one items through the air we breath, water we drink, food we eat, the drugs we consume, the cosmetics we use almost every day, the secondary smoke from smokers around and so on. These are all exposures in general, may be in small doses which may not bring about any noticeable responses. But when we get exposed to some chemical or a poison and experience some untoward response from the body, the exposure become acute exposure to the particular chemical or poison.  Acute exposure of a poison at a small dose may not result in any harm to the body but exposure to even a very small dose of hydrogen cyanide will bring death. Acute toxicity response can be a result of a single dose or multiple doses during a day or 24 hrs and may be without knowledge of what the Toxin to which the exposure is made. On exposure to small doses/ an acute exposure to a hazardous material may initiate symptoms like nausea, vomiting, stomach pain, head ache, irritation of skin and eye, cough, edema, seizures, respiratory failure etc. Toxicity data on almost every existing chemicals and xenobiotics are available. These data is arrived at after carrying out experiments in Laboratory animals.  

28/12/18

 

Classes on Toxicology: Chronic Exposure

In our day today life we may be exposed to some material each day repeatedly for over a period of time for more than 90 days, it may be called a chronic exposure. This may be due to work conditions, environmental conditions, or may be due to modern life style or use of certain drugs eg. for Asthma. These materials may be hazardous or debilitating in the long run. Exposure to lead or mercury through food or water, pesticides during agriculture work  or the vehicle solvents in many inhalation drugs. These kinds of chronic exposures to low concentrations have deleterious effects of living systems, symptoms slowly developing and expressing. The symptoms expressed owing to a chronic exposure may not subside as soon as the exposure is with held or stopped. These symptoms may be the outcome of the toxic or hazardous nature of the material to which the exposure is made. Hazardous substance need not always be a toxic material or a poison. Fibrosis of liver due to consumption of alcohol, kidney problems due to slow lead poisoning, neurological problems due to mercury poisoning, chronic bronchitis of chain smokers, fibrotic lung disease of coal workers, cancer of asbestos miners are some examples of chronic toxicity outcomes. Drugs for asthma, blood thinners, pain killers, thyroid problems are some examples which people take without medical supervision and end up in chronic exposure resulting in untoward results.

04/01/2019

Classes on Toxicology: Testing

Today we will try to understand “Testing” in the toxicology field.

Testing for poisonous materials in humans or animals, which are consumed  orally, inhaled or absorbed through the skin or injected parent erally is the common practice. This is for ascertaining the quantity if the suspected material is known, if not known for identifying the material too. This type of toxicology testing is also known as toxicology screening. Toxicology screening is very common in suspected poisoning in individual case, industrial settings, sports and games, drug abuse, clinical settings etc. Toxicology testing carried out on a dead body is Forensic Toxicology. Routine Toxicology testing is carried out by drawing samples of Urine and Saliva. Forensic Toxicologists use also use body/ organ fluids, cells, tissue etc. for testing. “Toxicity Tests” have another explanation. If a chemical or consumer product has to get a license to sell or commercial use, it has to undergo a battery of tests to prove it is not hazardous and safe to use. These tests are set up by FDA or EPA and used by the manufacturers of the product. They submit their test samples to accredited testing Laboratories for carrying out toxicology Tests or for Toxicology screening of their products. In the next class we will go through some of the glossary in Toxicology, which will make us understand the topics we have read through so far.

11/01/19

Classes on Toxicology : Glossary of terms used in toxicology, 2nd edition (IUPAC Recommendations 2007)

J. H. DUFFUS et al

Glossary

absolute lethal dose (LD100) Lowest amount of a substance that kills 100 % of test animals under defined conditions.

absolute lethal concentration (LC100) Lowest concentration of a substance in an environmental medium which kills 100 % of test organisms or species under defined conditions.

absorbed dose (of a substance) internal dose Amount (of a substance) taken up by an organism or into organs or tissues of interest.

absorption (in biology) uptake Penetration of a substance into an organism and its cells by various processes, some specialized, some involving expenditure of energy (active transport), some involving a carrier system, and others involving passive movement down an electrochemical gradient. Note: In mammals, absorption is usually through the respiratory tract, gastrointestinal tract, or skin into the circulatory system and from the circulation into organs, tissues, and cells.

absorption (of radiation) Phenomenon in which radiation transfers some or all of its energy to matter which it traverses.

absorption, systemic Uptake to the blood and transport via the blood of a substance to an organ or compartment in the body distant from the site of absorption.

abuse (of drugs, substances, solvents, etc.) Improper use of drugs or other substances.

accidental exposure Unintended contact with a substance or change in the physical environment (including, e.g., radiation) resulting from an accident.

activation (abiotic) Conversion of a xenobiotic to a more toxic derivative by modification not involving biological catalysis

active ingredient. Component of a mixture responsible for the biological effects of the mixture.

active metabolite. Metabolite causing biological and (or) toxicological effects.

active transport Movement of a substance across a cell membrane against an electrochemical gradient, in the direction opposite to normal diffusion and requiring the expenditure of energy.

acute Antonym:

  1. Of short duration, in relation to exposure or effect; the effect usually shows a rapid onset.

2. In clinical medicine, sudden and severe, having a rapid onset.

acute effect. Effect of finite duration occurring rapidly (usually in the first 24 h or up to 14 d) following a single dose or short exposure to a substance or radiation.

acute exposure. Exposure of short duration.

acute toxicity. 1. Adverse effects of finite duration occurring within a short time (up to 14 d) after administration of a single dose (or exposure to a given concentration) of a test substance or after multiple doses (exposures), usually within 24 h of a starting point (which may be exposure to the toxicant, or loss of reserve capacity, or developmental change, etc.). 2. Ability of a substance to cause adverse effects within a short time of dosing or exposure

acute toxicity test short-term toxicity test Antonym: chronic toxicity test Study in which organisms are observed during only a short part of the life span and in which there is often only a single exposure to the test agent at the beginning of the study.

 18/01/19

Classes on Toxicology : Glossary List 2

I am indebted to the copying of  Glossary of terms used in toxicology, 2nd edition (IUPAC Recommendations 2007) to Sree J. H. DUFFUS et al. Thanks are expressed here to the  respected Authors and Publishers.

Adelaide Calisto Fernandez.

 

absolute lethal dose (LD100) Lowest amount of a substance that kills 100 % of test animals under defined conditions.

absolute lethal concentration (LC100) Lowest concentration of a substance in an environmental medium which kills 100 % of test organisms or species under defined conditions.

absorbed dose (of a substance) internal dose Amount (of a substance) taken up by an organism or into organs or tissues of interest.

absorption (in biology) uptake Penetration of a substance into an organism and its cells by various processes, some specialized, some involving expenditure of energy (active transport), some involving a carrier system, and others involving passive movement down an electrochemical gradient. Note: In mammals, absorption is usually through the respiratory tract, gastrointestinal tract, or skin into the circulatory system and from the circulation into organs, tissues, and cells.

absorption (of radiation) Phenomenon in which radiation transfers some or all of its energy to matter which it traverses.

absorption, systemic Uptake to the blood and transport via the blood of a substance to an organ or compartment in the body distant from the site of absorption.

abuse (of drugs, substances, solvents, etc.) Improper use of drugs or other substances.

accidental exposure Unintended contact with a substance or change in the physical environment (including, e.g., radiation) resulting from an accident.

activation (abiotic) Conversion of a xenobiotic to a more toxic derivative by modification not involving biological catalysis

active ingredient. Component of a mixture responsible for the biological effects of the mixture.

active metabolite. Metabolite causing biological and (or) toxicological effects.

active transport Movement of a substance across a cell membrane against an electrochemical gradient, in the direction opposite to normal diffusion and requiring the expenditure of energy.

acute Antonym:

  1. Of short duration, in relation to exposure or effect; the effect usually shows a rapid onset.

2. In clinical medicine, sudden and severe, having a rapid onset.

acute effect. Effect of finite duration occurring rapidly (usually in the first 24 h or up to 14 d) following a single dose or short exposure to a substance or radiation.

acute exposure. Exposure of short duration.

acute toxicity. 1. Adverse effects of finite duration occurring within a short time (up to 14 d) after administration of a single dose (or exposure to a given concentration) of a test substance or after multiple doses (exposures), usually within 24 h of a starting point (which may be exposure to the toxicant, or loss of reserve capacity, or developmental change, etc.). 2. Ability of a substance to cause adverse effects within a short time of dosing or exposure

acute toxicity test short-term toxicity test Antonym: chronic toxicity test Study in which organisms are observed during only a short part of the life span and in which there is often only a single exposure to the test agent at the beginning of the study.

Next three weeks You will be getting 3 questions each covering the Classes we have already read through. Kindly answer them and send to me.

01/02/2019

Kindly answer these Questions and send them to me in a week’s time.The persons following the Classes on Toxicology and takes up the Tests through this Course will be given a Certificate of Proficiency signed by me. Three questions will be given each week starting from 1/2/2019.

1.What is Toxicology?

2.Who are the important personalities in Toxicology?

3.What are Xenobiotics?

 

Kindly answer these Questions and send them to me in a week’s time.

The persons following the Classes on Toxicology and takes up the Tests through this Course will be given a Certificate of Proficiency signed by me. Three questions will be given each week starting from 1/2/2019.

4.What is meant by a Dose?

5.What is Exposure?

6.What is Response ?

08/02/2019

 

Kindly answer these Questions and send them to me in a week’s time.

The persons following the Classes on Toxicology and takes up the Tests through this Course will be given a Certificate of Proficiency signed by me. Three questions will be given each week starting from 1/2/2019.

7.How Dose and Response related?

8.What is meant by Acute exposure?

9.What is meant by Chronic exposure?

15/02/19

 

Dear colleagues

Those who have not answered the three batches of Questions in Toxicology can get a week for answering them. Regular topics in Toxicology will continue from next week.

Regard

acf

23/02/19

 

Revision of the last classes in Toxicology

 Classes on Toxicology has so far covered topics like, An Inroduction to Toxicology, History of Toxicology, Classification of Toxicology, Xenobiotics,  Doses, Exposure, Response, Dose and response, Acute exposure, Chronic exposure, Testing. We have understood very important key words in Toxicology and also meaning of some common words used in Toxicology. The number of persons took the exam was not very high but quiet encouraging to a teacher. I request the readers of toxicology classes to clear their doubts every Saturday itself, ie. no postponements.

Next week on words we will continue with the Classes on Toxicology.

Regard

acf

09/03/2019

 

Classes on Toxicology  :_- Testing an Introduction

In our class we learned that what is testing in toxicology meant. Today we will try to see what is Toxicological Testing. We use  food, water, air, drugs, cosmetics, cleaners, perfumes, dress materials, materials for residents and offices, materials for transport vehicles, materials for air conditioning and keep the air tight compartments livable. We use different kind of fuels for various purposes, we use atomic power for discrete uses and so on. We have come a long way from our ancestry of the jungle and may be getting ready for a future which we may not be able to dream today. Finally we use medical devices as life saving products which amounts to more than sixty thousand in numbers under Medical prescription. In all these , the materials have to be safe to be used. In the earlier classes we have noted divisions in toxicology In the next week we will go into the details of Testing of Medical Devices.

15/03/19

Classes on Toxicology :- What is a Medical Device

A medical device is a man made material or objects to alleviate or replace the functions of any body organ/ systems, with out deforming or chemically degenerating or acted upon by body tissues and fluids. In this way medical devices are differentiated from drugs other chemical formulations.

While carrying out the intended activities a medical device becomes a Xenobiotic or foreign body and naturally invokes body response. These responses can be in the form of irritation, inflammation, necrosis, sensitization, cancer etc. and end up in the removal of the medical devices.

Therefore the materials that go into the fabrication have to qualify that they do not invoke body responses. Above we have noted only the general responses. Body responses to various biomaterials differ depending upon the nature and intended activity of the device as well as the different materials go into the fabrication of each medical devices specifically. Devices that act only on the surface of the skin, devices that penetrate the skin, devices that are going to stay for hours or days such as catheters, dialysis tubes, saline and blood distributing tubes, stents, heart valves etc. gives an idea of different type of medical devices. Dental materials, artificial dentures, contact lens other correctional devices for eyes, artificial hip, bones and knuckles, man made vertebra etc. are in common use at present.

We will look into various methods used to assure safety of these man made materials next week.

22/03/10

ACF.

Classes on Toxicology : Testing of Medical devices 

 Medical devices are life saving devices and it is mandatory that they should not impose any health hazard to the user whether it is a human or animal. As we know medical devices are classified as per their use and nature of contact with the body. The length of time the medical device is used, whether its contact with the body is superficial or invasive, whether it is active with in the body or contains medications etc. etc. are to be considered when the tests necessary for screening them for safety. Contact of devices with the body less than 24 hrs is Limited duration, more than 24 hrs and up to 30 days, Prolonged duration, more than 30 days, considered Permanent. So it is going to be different for different medical devices. Today we will look into the basic tests applied for Medical Device safety screening.

In the present scenario whenever a material comes for Toxicological testing it comes along with a comprehensive, Performance testing report,  Material characterization report, ASTM Certificates from material procurement agency etc. will give the Toxicologist ample information to decide upon the different tests warranted for Toxicological testing.

Cyotoxicity, Irritation, Sensitization, Intracutaneous reactivity,Systemic Toxicity, Genotoxicity, Implantation, Haemocompatibilty, test for Biological reactivity, Pyrogen are the basic toxicology tests from which Toxicologist will select  screening tests that a medical device under consideration has to undergo.

Each of the above tests will use the extracts of the Test sample, strips of the test samples for carrying out various Toxicological Tests.

29/03/2019

Classes on Toxicology 542019 :- Invitro Cytotoxicity tests for Medical devices

Medical devices are life saving devices and must be free of any kinds of hazards. Each device has a specific place to be used and serve the life supporting function. The nature of service may be in direct contact with the body tissues or indirect contact. Here the device has to be neutral to the biological action elicited by the body or body tissue and carry out the intended function. This nature of the device is termed as Biocompatibility. Each and every medical device has to be biocompatible and therefore has to undergo a battery of tests as we have noted in the last week’s class. Generally Cytotoxicity test is carried out as a primary screening test to weed out test samples which may turn out to be toxic in standard  biocompatibility testing in animals. International standards are available for Cytotoxicity testing.  National standards have to be streamlined with International standards and it will need time, money and  co operation among Nations around the World to carryit out. It is yet to be ascertained about the correlation of the Cytotoxicity test results with other Toxicological tests. There is difference of opinion that Cell culture systems used for carrying out cytotoxicity test does not mimic the living tissue systems in metabolism, scavenging and energy supply systems. Further there is no unanimity in methods of assessing the Cytotoxic response.

 In Cytotoxicity tests the test samples are prepared as per the test method followed. For direct method these samples are sterilized and placed on the surface of tissue  or cells in the petridishes. For indirect contact the test samples are extracted as per the method chosen to follow and these extracts are placed over the cell layers prepared for the test. Then these cells in culture dishes are observed as per the test method for cell growth /damage, cell counts, changes in morphology, biochemical changes are noted  and recorded to calculate the result of the test.

Note: in the next class we will go through the  basic principle applied universally for sample preparation for Toxicological  testing of various biomedical samples.

 05/04/19

Classes on toxicology:-  Sample preparation

The materials that go into the fabrication of Medical devices as well as the completed Devices has to undergo Testing for toxicity and safety, before going into the market. Depending on the end use, medical devices are grouped into different classes. Medical devices in each class has to undergo a set of Toxicological tests to pass the safety or nontoxic criteria. We have earlier noted about the different types of test that are applied to the Testing. For carrying out these tests samples are required. Candidate materials that go into the fabrication are of different size and shapes varying from powder, granules, strips, sheets, tubes, wires etc. Likewise the manufactured devices are also of different size, shapes, tubes, powders, pastes etc. Further medical devices are designed, fabricated and tested in various countries by many different companies. Therefore standardization of tests and test sample requirements for each test is a necessity and these are drawn up and published by International organization for Standards generally known as ISO. This is a group formed by members drawn from various organization of Standards of different Countries, especially European. Food and Drug Administration, USA is another organization which sets standards for design, fabrication, testing and certification, safety and hazard notification of Medical Devices, American Society for Testing of materials is yet another organization for setting up Standards for materials that go into the fabrication of medical devices as well as the testing of safety of medical devices, Bureau of Indian Standards is the Indian counterpart setting up standards. Therefore to get the details of sample preparation one can refer to the particular standard he wants to follow. Depending on the test to be carried out test samples could be used directly as in the case of Implantation test or sensitization test or indirectly as extracts of test materials as in the case of Systemic toxicity or Pyrogen tests. The various Standards specify the appropriate amount of test materials or amount and nature of extraction mediums and the temperature at which extractions should be carried out. The untoward response of test samples arise from leachable ingredients contained in that sample. When samples are directly tested these ingredients if present may leach into the test system to express untoward response. In the indirect system the untoward ingredients will leach into the extraction medium which in turn will express toxic response in the test system. The nature and site of use of medical device, the temperature at which it is manufactured, sterilization methods it has to undergo, the recommended storing conditions etc. etc. of each medical device have to be considered while selecting test methods and extraction conditions. Sodium chloride for injection(SCI) (USP,IP) Vegetable Oil (USP, IP,)1/20 alcohol in SCI, Dimethyl sulfoxide ( DMSO), Polyethylene glycol 400(PEG) are the common extraction media used. Other clinically relevant media may be used along with reasons for the choice. 37,50,70,120 degree centigrade are the commonly used temperatures for carrying out extraction depending on the nature of the test samples and the selected medium for extraction. Test samples are generally taken by surface area for extraction tests. 6 cm2 area if the thickness is 0.5 mm and 3cm2 if the thickness is more than 0.5 mm. per ml.You may note that material requirement for each test vary and the International and National Standards give detailed picture of sample requirement and kindly look at them carefully. Cytotoxicity, blood compatibility, mutagenicity, genotoxicity tests are carried out the sample requirement and test conditions are very specific and may change with the nature of the sample to be evaluated.

Kindly call or E- mail your queries so that I can get back to you.

12/04/19

Classes on Toxicology:- Sensitization Test

Some of as allergic to dust, pollen, house hold or Office Keys, milk, some food etc. once we are allergic to some material or chemical in a material we avoid them. But if we happened to be in contact with them unknowingly we get allergic symptoms and if the contact is repeated the symptoms will be moving up the scale like moderate to severe and science say that you are sensitized to that particular material. Sensitization episodes can become fatal too. The medical devices are made up of various materials and it is imperative that the candidate material as well as the end products should be negative in Sensitization Tests. Most of the sensitization reactions to biomaterials have been noted as the dermal cell mediated rather that humeral or antigen antibody responses. Dermal sensitization reactions in laboratory animals are marked by redness and swelling. Sensitization reactions in humans appear only after continued use of a biomedical device such as permanent implants or use of natural latex gloves. These sensitization responses may be the result of a chemical eluted from the device that is an allergen, over a period of time.

Summary of the tests are given below as quoted from ISO documents:

TEST METHODS

Biomaterials and other device materials are tested for the presence of sensitizing chemicals using guinea pigs, a species known to be nearly as responsive to dermal sensitizers as human beings are. Guinea pig sensitization tests require six to eight weeks and thus take the longest time to complete of all the acute biocompatibility tests described in the 10993 standards.

The repeated-patch, or Buehler, test method involves exposing the shaved backs of guinea pigs directly to the test material under

occlusive dressings for a minimum of six hours. This procedure is repeated as many as three times a week for three weeks. This part of the test is often referred to as the induction phase. Following a two-week rest or recovery period to allow for the development of a delayed response, the animals are challenged by a final exposure to a patch of the biomaterial. The repeated-patch model is used primarily for topical devices such as dermal electrodes and surgical gowns and drapes, since in these cases the method of applying test materials to the animals simulates clinical use.

In the maximization, or Magnuson-Kligman, test method, fluid extracts of the test material are prepared in saline and vegetable oil, and separate groups of guinea pigs are exposed repeatedly to the two types of extracts. The guinea pigs are first injected with an extract along with an adjuvant intended to enhance an immune response, then receive a topical application. Following a two-week rest or recovery, the animals are covered with a topical patch containing the extract. Generally considered more sensitive than the repeated- patch model, the maximization test is used for device materials that will contact areas other than skin. The use of both a saline extract and an oil extract simulates extraction by bodily fluids and by intravenous liquids and other pharmaceutical products that first contact the device and then the patient.”

It will be a good idea to read through the ISO standards for sensitization tests. See you next week.

03/05/2019

Classes on toxicology:- Test for Irritation

1-Intracutaneous Irritation Test

Irritation test is carried out to prove that the candidate material supplied for biocompatibility testing is a non irritant material in the in vivo test system. We know that this material has undergone the in vitro cytotoxic test and gave negative results. Test samples are extracted in fluids selected at a given ratio of surface of the candidate material at controlled conditions of time and temperature. Two albino rabbits are selected and their dorsal side is clipped free of hair and free of cuts or aberrations. Recommended volume of extract is intracutaneously injected on different sites on one side and equal number of sites are injected with a control solution intracutaneously. Toxicologist selects the type of the extracts that should be used considering the nature and end use of the candidate material. At 24, 48 and 72 hrs after the injection the injected sites are observed and scored for skin response towards the test extracts. Parameters observed are redness, swelling and necrosis. In some cases heat and pain may result after the injection. Observed results are then compared with the skin response towards the control injections. The response is rated as none, mild, moderate and severe and indexed as per the standard that is used for Guidance in carrying out the test. This test is mandatory for Medical devices so as to avoid skin, mucosal and eye irritation. Though the candidate material may be non irritant, but irritation maybe due to unintentional contaminants from mould releasing agents,remnants traces of cleaning or chemical sterilents used or even from the packing materials.

 2- Primary skin irritation test.

 In the Intracutaneous irritation test,  test extracts prepared under selected conditions of temperature and time is used and is considered a comprehensive test to get any irritant leachables from the candidate test material. In the primary skin irritation test the candidate material itself is exposed directly to the skin for different periods of time. For this test two albino rabbits with their dorsal side shaved are used. The samples placed on the back skin are held in place with occlusive patches. In some instances the Toxicologist may go for applying extracts instead of patches after giving reason for changing the nature of test. The observation period stars from 4 hours to 72 hours. The sites are observed for erythema (redness), edema(swelling/inflammation) and rated as mild, moderate, severe etc. The preparation of samples, size or quantity of samples, observation periods, rating of results etc. will vary with the standard one chose to follow. Occular irritation test. This a variation of the Intracutaneous irritation and the Primary skin irritation tests. This test is specifically recommended for drugs and Medical devices that will be in contact with the eye. Rabbits are the test animals. In the initial test only one animal is used for test. In order to confirm the results two more animals can be used. The lower eye lid of one eye is drawn out a little to produce a small pocket like sac and the test sample is placed in this pocket. The other eye serves as control. Use of extract or powder or solid is determined by the toxicologist and the Standard he chose to follow. Eye is evaluated for the erythema, especially of the Conjunctiva, response of iris to light, corneal opacity, nature of discharge from the eye. As in the above cases the period of observation is 24 to 48 hours and rating is carried out as in the guideline that is followed.

Classes on Toxicology:-  Systemic Toxicity.

Systemic toxicity is the adverse effect of a material or chemical in a living system caused by the material to various body organs and organ systems through the circulatory or lymphatic systems from the place of entrance ie skin, inhalation, oral, intravenous. Likewise a biomaterial or medical device placed in the human being may exert adverse effects at distant places with in the body or organ tissue. These effects are termed acute, short term, long term or chronic depending on the nature of the response of the medical device in question. Medical devices are generally not soluble or do not change structure, shape, size or degrade while serving the intended function. But if they are not biocompatible materials leaching from them may systemically reach distant body sites as eyes, lungs, liver, kidney, brain etc. to cause various adverse effects.

In order to produce safe Medical devices the candidate materials that go into the fabrication of these medical devices and the end products are subjected to systemic toxicity tests. Depending upon their intended use and site of use they are subjected to standard systemic test for acute (up to 24 hrs), sub acute(14 to 28 days), sub chronic (up to 90 days)and chronic( up to animals life span) periods of observation after the initiation of the test. Mice and rats are commonly used for systemic toxicity studies but rabbits, dog or an appropriate animal can be used for test after giving valid reasons for the same by the investigator and approval by the Institutional animal’s ethics committee.

For systemic toxicity studies the test samples are selected and extracts prepared as described earlier using appropriate extracting media at required temperature. The route of exposure is decided by the investigator considering the end use and period of use of the medical device. The observation parameters and other data like blood picture, serum chemistry, urine analysis, histopathology of major organ systems will be carried out and recorded as per the work procedure accepted. Long term or chronic tests are also carried out the same way and to prove that the use of the tested device is safe in every respect. Infact the Implantation test, and Pyrogen test that are coming next in line to be explained could be called systemic test because the response to these tests could be local in the test site as well as in distant body organs or behavior. The systemic test could be carried out as per ISO1993 to get worldwide recognition for the results.

10/05/19

Classes on Toxicology:- Implantation Test

Implantation test is carried out by placing test samples of candidate Biomaterials or end product of Medical Devices into the test sites of living laboratory animals  in order to find out the response of the surrounding tissue to the test samples. Test samples are generally of 1x1x10mm size and placed into the tissue using a trocar and needle of 18 or 19 gauge size. The paravertebral muscle of the rabbits are the standard site of Implantation test. Healthy albino rabbits of body weight of less than 2.5 kg are chosen for test. The period of observation depends on the end use of the end product and decided by the investigator. The test samples for implantation test are implanted on one side of the paravertebral muscles and the negative samples or control samples on the contralateral side. The test samples and implantation needles are sterilized and the paravertebral muscle on the both sides of the vertebral column clipped and sterilized with 70% alcohol or beta iodine solution. The animals are anaesthetized for implantation and the procedure carried out by a Veterinarian. The animals are observed for 72 hours for health and normal behavior and sacrificed giving an overdose of an anaesthetic. The test samples are recovered along with surrounding tissue for immediate macroscopic evaluation and after scoring the results the samples are fixed in 10% formalin or recommended solutions for histopathological studies and scoring. Depending on the end use of the end product or Medical device the observation periods may be extended up to 12 weeks. In the cases of special devices the site of implantation could be chosen as subcutaneous, bone, ocular, dentine, brain, mucosal etc. and the observation periods also will vary as per the decision of the investigator and depending on which Standard is being followed for Testing. From mice and rat to any species could be used for testing. Full procedure kindly do refer USP or ISO10993 standards.

17/05/19

Comments are closed