Series 1: General Toxicology: TOXICOLOGY Question and Answer bank by Prof (Dr) Pawan K (PK) Gupta

General Toxicology: TOXICOLOGY Question and Answer bank

INTRODUCTION

TOXICOLOGY Question and Answer bank is aimed to make the study of toxicology simple and understandable through illustrations, images, custom made drawings, self-explanatory tables, and questions and answers collated from standard and authoritative textbooks, and widely scanned. The author’s own experience in different branches of toxicology including environmental and veterinary toxicology has been abstracted in these series of articles. This is first articles of series. The article has been written in a manner to stimulate interest on various facets of the subject and make it more exciting. It is general experience that theoretical description does not attract as much attention and interest as the illustrations and images. At the same time the information learnt through questions and their satisfactory replies make the topics easier to grasp them.

The book provides comprehensive quick reference for various examinations. However, it should be noted that this series serve only as a supplement and not as a replacement for any textbook and class room learning.

The series is expected to cover several topics such as general toxicology, principles of toxicology, risk assessment, disposition, mechanism of toxicity, toxic effects of various xenobiotics, poisonings of poisonous and venomous organisms, plant toxins, poisonous and food poisonings, radiation hazards and, abuse of drugs. The following series will also the adverse effects on environment and ecosystem exposed to various toxicants and poisonings as relevant to domestic and other animals.

Each article will be in the format of questions and answers, multiple choice questions, true and false statements or correct/ incorrect statements, fill in blanks, and matching the statements that will be useful for students, teachers and practicing in medical sciences, toxicology, pharmacology, medicine, pharmacy, environmental toxicology and in veterinary sciences.

WHO will be benefitted

The author believes that these series would be:

Ø          A good alternative to be used for various courses and an excellent contribution for the students who needs a study aid for toxicology but wants more than a textbook as they need a self-testing regime.

Ø                The teachers of toxicology who needs inspiration when composing questions for their students.

         The established toxicologists who wants to test their own knowledge of understanding

the subject matter.

Ø  Will be useful at universities and colleges, in industry for in-house training courses in toxicology which I know exist in some pharmaceutical and chemical companies

Ø  Required for studying for the toxicology Boards and for preparation of different examinations.

Thus, the main strength of the series will reflect the breadth and multi-disciplinary nature of toxicology with illustrative approach to the subject that is needed to improve engagement with and understanding of the subject having a very wide audience.

Toxicology is a rapidly evolving field. Suggestions and comments are welcome to help the author improve the contents of the series. Please also suggest or send comments at drpkg_brly@yahoo.co.in or drpkg1943@gmail.com

GENERAL TOXICOLOGY

Q. What is toxicology?

Toxicology is the study of the adverse effects of chemicals or physical agents on living organisms. The word  ‘toxicology’ is derived from the Greek word ‘toxicon’ which means ‘poison’ and logos means to study. It also includes study of special effects of toxicants developmental toxicity, teratogenicity, carcinogenicity, mutagenesis, immune-toxicity, neurotoxicity, endocrine disruption, etc.

Q. Who is the father of rational medicine?

Hippocrates (460-375 BC) is regarded as the “Father of Rational Medicine”. He created the Hippocratic oath. He believed that disease came naturally and not from superstitions and GOD. He advocated hot oil as an antidote in poisoning and induced vomiting to prevent absorption of the poisons.

Q. What do you know about Paracelsus?

Hohenheim-Paracelsus (1493–1541) a first century Roman physician, who promoted a focus on the toxicon, the toxic agent, as a chemical entity. He recognized the dose-response concept and in one of his writings stated, “All substances are poisons, there is none which is not a poison. The right dose differentiates a poison and a remedy”. 

Q. Who is Friedrich Serturner? What is his contribution?

Friedrich Serturner (1783-1841), German pharmacist who isolated the specific narcotic substance from opium and named as morphine after Morpheus, the Roman God of sleep.

Q. Who is a Father of Toxicology?

M J B (Mattie Josesph Benaventura) Orfila (1787-1853), a Spanish physician is a considered as “Father of Toxicology”.

Q. Describe main contributions of M J B Orfila (1787-1853).

He established toxicology as a discipline distinct from others and defined toxicology as the study of poisons. He advocated the practice of autopsy followed by chemical analysis of viscera to prove that poisoning has taken place. His “treatise” Traite des Poisons published in 1814 laid the foundations of forensic toxicology.

Q.   Who is father of experimental pharmacology? Describe in brief his contributions.

Francois Magendie (1783-1855) is known as the “Father of Experimental Pharmacology”, a pioneer French physiologist and toxicologist studied the mechanism of action of emetine, morphine, quinine, strychnine and other alkaloids.

Q. Who was Claude Bernard?

Claude Bernard (1813-1878) was a French physiologist who is considered the "Father" of Modern Experimental Physiology. Claude Bernard's first important works were carried out on the physiology of digestion, particularly the rôle of the pancreas exocrine gland, the gastric juices and of the intestines. In addition to this, Bernard also made other important contributions to the neurosciences.

Q. Who was Louis Lewin (1854-1929)?

Louis Lewin (1854-1929) was a German scientist who took up the task of classifying drugs and plants in accordance with their psychological effects. He also published many articles and books dealing with toxicology of methyl alcohol, ethyl alcohol, chloroform, opium, and some other chemicals. His important publications are “toxicologist’s view of world history” and “A textbook of toxicology”.

Q. Who discovered the insecticidal properties of DDT? What is his major contribution?

Paul Hermann Muller in 1939 discovered they of insecticidal properties of dichlorodiphenyltrichloroethane (DDT) .He was awarded Nobel Prize in 1948 “for his discovery of the high efficiency of DDT as a contact poison against several arthropods”.

Q. Who is “Father of Nerve Agents”?

Gerhard Schrader (1903-1990) was a German chemist who accidentally

Health for all: Penta poisoning

Overview of Pentachlorophenol Poisoning (Penta poisoning)

Pentachlorophenol (PCP), commonly known as penta, has been used as a fungicide, molluscicide, insecticide, and wood preservative. Its use is now permitted only for industrial purposes; agricultural and domestic uses are prohibited, because it is classified as a highly hazardous pesticide.

The oral LD₅₀ of penta in rats is 150–210 mg/kg body wt. Common signs of poisoning include nervousness, rapid pulse and respiratory rate, weakness, fever, muscle tremors, convulsions, loss in righting reflexes, and asphyxial spasms followed by death. Corneal injury may result from splashes or vapor overexposure. Chronic poisoning results in emaciation, fatty liver, nephrosis, and weight loss.

The persistence of penta in soil and water and apparent widespread use has resulted in significant exposure to animals. Young swine have died after dermal exposure to freshly penta-treated wood used in farrowing crates or farrowing houses. In vivo studies in swine demonstrated that exposure to penta-contaminated soil can result in significant dermal absorption of the pesticide. Penta can be absorbed through intact skin and lungs and is an intense irritant to the skin and mucous membranes. Penta absorption in skin was greater in water or water-based mixtures than in 100% ethanol. Because animals typically have access to water at all times, this hydrophilic characteristic of penta suggests enhanced dermal absorption.

When absorbed, penta increases metabolism by uncoupling cellular phosphorylation. Animals fed in troughs made of lumber treated with PCP may salivate and have irritated oral mucosa. Both penta and its major metabolite, tetrachlorohydroquinone (TCHQ), can induce epidermal hyperplasia in mice.

Poultry have been exposed to sawdust and shavings from penta-treated wood. Associated adverse effects include reduced growth rates, kidney hypertrophy, and decreased humoral immune response. Penta exposure can also result in an off-taste to eggs and meat as a result of degradation of chlorophenols to chloroanisols. Vaporization or leaching of penta in pens, enclosures, homes, and barns has caused illness and death.

Cattle and pigs exposed to wood treated with commercial grade penta had increased mortality, possibly decreased fertility in boars, and reduced productivity (milk, meat, etc). The lethal dose in cattle and sheep is ~120–140 mg/kg body wt.

Commercial lots of technical-grade penta contain small but biologically significant amounts of highly toxic impurities such as chlorinated dioxins and dibenzofurans, tetrachlorophenols, and hydroxychlorodiphenyl ethers; these compounds can exert their own effects such as early fetotoxicity. Commercial-grade penta causes hepatic porphyria, increased microsomal monooxygenase activity, and increased liver weight. Pure penta was not teratogenic in rats.

Penta can cause residues in animal tissues. Also, a significant amount of hexachlorobenzene is metabolized in animal tissues to penta. Pentachlorophenol is considered to be a carcinogen and a tumor promoter, although studies have shown that the pure material does not increase the incidence of tumors in rats and mice. The technical-grade material has also been shown to be immunotoxic in laboratory studies. Penta must be handled very carefully and kept away from animal contact.

Whole blood analysis for penta may aid in the diagnosis of poisoning; diagnosis is usually made on the basis of the signs and the proximity of treated lumber in the animal’s environment.

There is no known antidote. Termination of exposure, bathing dermally exposed animals, oral administration of activated charcoal, and supportive therapy may be indicated. Bathing should be done gently with cold water and detergent so as not to cause vasodilation and increased absorption. Antipyretics, eg, aspirin and acetaminophen, should not be used. Treatment involves cooling the animal and administering fluids, electrolytes, and anticonvulsants. Read more --------

Overview of Pentachlorophenol Poisoning - Merck Veterinary Manual

www.merckvetmanual.com › Toxicology › Pentachlorophenol Poisoning

By P. K. Gupta, PhD, Post Doc (USA), PGDCA, MSc VM & AH BVSc, FNA VSc, ... FAEB, FACVT (USA), Gold Medalist, Editor-in-Chief, Toxicology International.

The Merck Veterinary Manual (2016). Chapter “Pentachlorophenol Poisoning” by PK GUPTA 11^th edition, Merck & Co. Inc Whitehouse Station, NJ, USA pp 3052-53

• Veterinary

·         Pentachlorophenol Poisoning

·         Overview of Pentachlorophenol Poisoning

Health for all: Overview of Herbicide Poisoning

Health for all: Overview of Herbicide Poisoning: prevention is better than cure

Herbicides are used routinely to control noxious plants. Most of these chemicals, particularly the more recently developed synthetic organic herbicides, are quite selective for specific plants and have low toxicity for mammals; other less selective compounds (eg, sodium arsenite, arsenic trioxide, sodium chlorate, ammonium sulfamate, borax, and many others) were formerly used on a large scale and are more toxic to animals.

Vegetation treated with herbicides at proper rates normally will not be hazardous to animals, including humans. Particularly after the herbicides have dried on the vegetation, only small amounts can be dislodged. When herbicide applications have been excessive, damage to lawns, crops, or other foliage is often evident.

The residue potential for most of these agents is low. However, runoff from agricultural applications and entrance into drinking water cannot be ruled out. The possibility of residues should be explored if significant exposure of food-producing animals occurs. The time recommended before treated vegetation is grazed or used as animal feed is available for a number of products.

Most health problems in animals result from exposure to excessive quantities of herbicides because of improper or careless use or disposal of containers. When used properly, problems of herbicide poisoning in veterinary practice are rare. With few exceptions, it is only when animals gain direct access to the product that acute poisoning occurs. Acute signs usually will not lead to a diagnosis, although acute GI signs are frequent. All common differential diagnoses should be excluded in animals showing signs of a sudden onset of disease or sudden death. The case history is critical. Sickness following feeding, spraying of pastures or crops adjacent to pastures, a change in housing, or direct exposure may lead to a tentative diagnosis of herbicide poisoning. Generally, the nature of exposure is hard to identify because of storage of herbicides in mis- or unlabeled containers. Unidentified spillage of liquid from containers or powder from torn or damaged bags near a feed source, or visual confusion with a dietary ingredient or supplement, may cause the exposure. Once a putative chemical source has been identified, an animal poison control center should be contacted for information on treatments, laboratory tests, and likely outcome.

Chronic disease caused by herbicides is even more difficult to diagnose. It may include a history of herbicide use in proximity to the animals or animal feed or water source, or a gradual change in the animals’ performance or behavior over a period of weeks, months, or even years. Occasionally, it involves manufacture or storage of herbicides nearby. Samples of possible sources (ie, contaminated feed and water) for residue analysis, as well as tissues from exposed animals taken at necropsy, are essential. Months or even years may be required to successfully identify a problem of chronic exposure.

In order to recognize whether a subject is exposed to herbicides, or even accidental poisoning, now standardized analytical procedure for diagnostic investigation of biological materials have become established and these are subsumed under the term“biomonitoring”. Accurately biomonitoring is an important tool that can be used to evaluate human or animal exposure to such herbicides by measuring the levels of these chemicals, their metabolites or altered biological structures or functions in biological media such as urine, blood or blood components, exhaled air, hair or nails, and tissues  The use of urine has advantage because of ease of availability.  As such urine has been used for biomonitoring of several herbicides such as 2,4-D, 2,4,5-T, MCPA (2-methyl-4-chlorophenoxyacetic acid), atrazine, diuron, alachlor, metolachlor, paraquat, diquat, imazapyr, imazapic,  imazethapyr, imazamox,  imazaquin and  imazamethabenz-methyl with the objective to assess exposure and health risk to exposed subjects.

If poisoning is suspected, the first step in management is to halt further exposure. Animals should be separated from any possible source before attempting to stabilize and support them. If there are life-threatening signs, efforts to stabilize animals by general mitigation methods should be started. Specific antidotal treatments, when available, may help to confirm the diagnosis. As time permits, a more detailed history and investigation should be completed. The owner should be made aware of the need for full disclosure of facts in order to successfully determine the source of poisoning, eg, unapproved use or failure to properly store a chemical.

Toxicity and Management of Poisoning

There are >200 active ingredients used as herbicides; however, some of them are believed to be obsolete or no longer in use. Of these, several have been evaluated for their toxic potential and are discussed below. More specific information is available on the label and from the manufacturer, cooperative extension service, or poison control center. Selected information on herbicides, such as the acute oral toxic dose (LD50) in rat, the amount an animal can be exposed to without being affected (no adverse effect level), the likelihood of problems caused by dermal contact in rabbit (dermal LD50, eye and skin irritation), deleterious effects on avian species and toxicity to fish in water is included for some commonly used herbicides (TABLE 1). Comparative toxic doses (TD) and lethal doses (LD), of selected herbicides in domesticated species such as monkeys, cattle, sheep, pigs, cats, dogs, chickens is also summarized (TABLE 2). The information is only a guideline because the toxicity of herbicides may be altered by the presence of other ingredients (eg, impurities, surfactants, stabilizers, emulsifiers) present in the compound. With a few exceptions, most of the newly developed chemicals have a low order of toxicity to mammals. However, some herbicides such as atrazine, buturon, butiphos, chloridazon, chlorpropham, cynazine, 2,4-D and 2,4,5-T alone or in combination, dichlorprop dinoseb, dinoterb, linuron, mecoprop, monolinuron, MCPA (2-methyl-4-chlorophenoxyacetic acid), prometryn, propachlor, nitrofen, silvex, TCDD (a common contaminant during manufacturing process of some herbicides such as 2,4- D and 2,4,5-T), tridiphane and tridiphane are known to have adverse effects on development of

Read more

Overview of Herbicide Poisoning

By P. K. Gupta, PhD, Post Doc (USA), Hon DSc PGDCA, MSc VM & AH BVSc, FNA VSc, FASc, AW, FST, FAEB, FACVT (USA), Gold Medalist, Editor-in-Chief, Toxicology International

The Merck Veterinary Manual (2016). Chapter “Herbicide Poisoning” by PK GUPTA 11^th edition, Merck & Co. Inc Whitehouse Station, NJ, USA  pp 2969-99

·         Herbicide Poisoning

·         Toxicity and Management of Poisoning

·         Overview of Herbicide Poisoning

·         Inorganic Herbicides and Organic Arsenicals

·         Organic Herbicides

Toxicity and Management of Poisoning

Steps to be undertaken to prevent cruelty to animals

The academy of sciences foe animal welfare is dedicated to the improvement of health and safety of humans and animals and also the protection of their environment.

To fulfill these objectives, the academy is committed to: 

a)       Critical goal in science and education will be continually identified.

b)      Research involving laboratory animal only if is necessary to ensure enhancement of human and animal health and protection of the environment. Scientifically valid research designed to reduce, refine, or replace the need for laboratory animals is encouraged.

c)       Research animals must be used in a responsible manner

d)      Each one shall observe the spirit as well as the ethical standards of treatment with regard to the welfare of humans and animals involved in any experimental procedure. Cruelty of any kind will be prevented, .

e)       Allocation of less painful or stressful procedures and improve animal care.

f)       The development and enforcement of alternatives to the use of animals. 

   

 Those who are dedicated to the cause of animal welfare can contact at 1asaw1943@gmail.com

Awards

Associate ship for Animal Lovers

All kind-hearted persons wish love and care affection for animals can become associates of this Academy by contributing a one-time fee. Academy of sciences foe Animal Welfare was duly constituted as per guidelines laid down by the Animal Welfare Board of India under the Ministry of Environments and Forests, Government of India. The associates are eligible to use a title of honor in abbreviation MASc (AW) along with their names.

Fellowship

Associates are eligible to become fellows. They will enjoy special privileges and will receive certificates from a dignitary and will be entitled to use a title of honor in abbreviation FA Sc (AW). Fellows will enjoy special privileges and can sponsor associates for fellowship of the academy.

For details visit site: animalwelfareindia.org

Management of Iron Deficient Anemia and Iron Toxicity

How We Can Prevent Anemia?

Consider the following groups

i)                 Pregnant women, women with menorrhagia,

ii)               Consumers of a strict vegetarian diet.

iii)            Infants,

iv)            Adolescent girls,

v)               and regular blood donors.

Pregnant women have been given supplemental iron often in the form of all-purpose capsules containing vitamins, calcium, and iron. If the patient is anemic (hemoglobin < 11 g/dL), administer the iron at a different time of day than calcium because calcium inhibits iron absorption.

Iron supplementation of the diet of infants is advocated. Premature infants require more iron supplementation than term infants. Infants weaned early and fed bovine milk require more iron because the higher concentration of calcium in cow milk inhibits absorption of iron. Usually, infants receive iron from fortified cereal. Additional iron is present in commercial milk formulas.

Iron supplementation in populations living on a largely vegetarian diet is advisable because of the lower bioavailability of inorganic iron than heme iron.

How Is Iron Deficiency Anemia Treated?

Diets high that include the following foods can help treat or prevent iron deficiency:

i)                  dark green, leafy vegetables

ii)               dried fruits

iii)            nuts

iv)            iron-fortified cereals

Additionally, vitamin C helps our body absorb iron.

Of the various iron salts available, ferrous sulfate is the one most commonly used.

Although the traditional dosage of ferrous sulfate is 325 mg (65 mg of elemental iron) orally three times a day, lower doses (eg, 15-20 mg of elemental iron daily) may be as effective and cause fewer side effects. To promote absorption, patients should avoid tea and coffee and may take vitamin C (500 units) with the iron pill once daily.

Claims are made that other iron salts (eg, ferrous gluconate) are absorbed better than ferrous sulfate and have less morbidity.

 If possible, one should take iron tablets on an empty stomach, which helps the body absorb them better. If they upset the stomach, one can take them with meals. One may need to take the supplements for several months. Iron supplements may cause constipation or stools that are black in color.

What about Parenteral Iron Therapy?

Reserve parenteral iron for patients who are either unable to absorb oral iron or who have increasing anemia despite adequate doses of oral iron.

What are Causes of Iron Poisoning or Toxicity?

1.    Acute iron poisoning from accidental ingestion of iron containing dietary supplements is the most common cause of acute toxicity. It most often occurs in children. Severe toxicity occurs after the ingestion of more than 0.5 g of iron or 2.5 g of ferrous sulfate. Toxicity occurs about 1–6 hours after ingestion.

2.    Inhalation of iron oxide fumes or dust may cause pneumoconiosis in occupational settings.

3.    Chronic iron toxicity from iron overload in adults is a relatively

common problem.

There are three basic ways in which excessive amounts of iron can accumulate in the body.

1.    Hereditary hemochromatosis due to abnormal absorption of iron from the intestinal tract. Hereditary hemochromatosis is an autosomal recessive disorder attributed to mutation in the hemochromatosis gene.

2.    Excess intake of iron through diet or from oral iron preparations.

3.    Repeated blood transfusions body iron can increase 10 times higher than normal

Symptoms of Toxicity

 abdominal pain,

diarrhea, and vomiting.

pallor or cyanosis,

metabolic acidosis,

and cardiac collapse.

Death may occur in severely poisoned children within

24 hours.

How We can Treat those Who get Toxicity Due to Iron?

• Consult the physician

General and specific treatment include:

• Supportive therapy to maintain adequate blood pressure and electrolyte balance is essential
• I.V. fluid resuscitation 20 mL/kg
• Potassium and glucose administration as necessary
• Desferrioxamine is a chelating agent that forms a water soluble desferrioxamine-iron complex

Importance of Iron –Essential Metal for our Body

Iron is an essential metal for our blood (erythropoiesis and a key component of hemoglobin, myoglobin, heme enzymes, metalloflavoprotein enzymes, and mitochondrial enzymes). In biological systems, iron mainly exists as the ferrous (2+) and ferric (3+) forms and is important

1.  in terms of iron deficiency,
2.  or toxicity

i)                  Due to accidental acute exposures,

ii)               Chronic iron overload (due to idiopathic hemochromatosis)

iii)            As a consequence of excess dietary iron

iv)            Due to frequent blood transfusions

                                                         

Iron metabolism is regulated by a complex series of events that maintain homeostasis,

i)                   mainly involving absorption,

ii)               storage,

iii)            and excretion.

Blood Iron comes mainly from meat, poultry, fish and other food sources such as green leafy vegetables.

For Non-heme iron, absorption is influenced by its solubility and by other dietary factors.

Essentiality and Deficiency

Do you know what is Iron Deficiency Anemia?

Iron deficient anemia occurs when iron level of red blood cells (RBCs) is lower than normal. This type of anemia is the most common type of anemia, and it occurs when our body doesn’t have enough of the mineral iron. Anemia is a common condition and can occur in both men and women of any age and from any ethnic group. Some people may be at greater risk for iron deficiency anemia than others. Iron deficiency is worldwide.

These include:

i)                  infants,

ii)               young children,

iii)            and women of child-bearing age.

Critical period for iron deficiency

In children is between the ages of 6 months and 2 years.

 In addition to anemia: Other effects are impaired psychomotor development and intellectual performance,

Decreased resistance to infection,

In adults adverse pregnancy outcomes, possibly increased susceptibility to lead and cadmium toxicity.

Causes for Iron Deficiency Anemia:

Iron is present in the blood protein called hemoglobin. This protein carries oxygen to our body’s tissues, which is essential for our tissues and muscles to function effectively. If our body does not have enough iron in the blood, the rest of our body does not get enough amount of oxygen for its proper function.

There are many reasons that can cause iron deficiency leading to anemia. These include:

1.    Inadequate Iron Intake

Iron is essential during for growth and development, pregnant women and young children and need even more iron-rich foods in their diet. Eating too little iron over an extended amount of time can cause a shortage in your body.

2.    Blood Loss Due to Menstruation, pregnancy and childbearing age

In women of childbearing age, the most common causes of iron deficiency anemia are heavy menstrual bleeding and blood loss during childbirth.

3.    Internal Bleeding

Internal bleeding can lead to iron deficiency anemia. Examples include an ulcer in your stomach, polyps (tissue growths) in the colon or intestines, or colon cancer. Regular use of pain relievers, such as aspirin, can also cause bleeding in the stomach. 

4.    Inability to Absorb Iron

Certain disorders or surgical procedures that affect the intestines can also interfere with absorption of iron.

The symptoms of moderate to severe iron deficiency anemia include:

·         general fatigue

·         weakness

·         pale skin

·         shortness of breath

·         dizziness

·         strange cravings to eat items that aren’t food, such as dirt, ice, or clay

·         a tingling or crawling feeling in the legs

·         tongue swelling or soreness

·         cold hands and feet

·         fast or irregular heartbeat

·         brittle nails

·         headaches

How Is Iron Deficiency Anemia Diagnosed?

A doctor can diagnose anemia with blood tests.

                                                                                  to be continued