Series 2: TOXICOLOGY Question and Answer bank-TOXICOLOGY by Prof (Dr) Pawan K (PK) Gupta

TOXICOLOGY Question and Answer bank  

(series 2)

                                                                                                             In continuation of  series 1st 

Q. What is REACH regulation?

REACH regulation is concerned with registration, evaluation, authorization and restriction of chemicals in European Union (EU). It entered into force on 1st June 2007. It streamlines and improves the former legislative framework on chemicals of the EU.

Q. Describe briefly the term “Toxicity rating”.

A system of “toxicity rating” has been evolved for common poisons. The higher the toxicity rating for a particular substance (over a range of 1-6), the greater is the potency. The toxicity rating based on toxic potential of substances. For example, super toxic, extremely toxic, very toxic, moderately toxic, slightly toxic and practically non-toxic.

Q. What do you mean by super toxic

Less than 5 mg/kg

Q. What do you mean by extremely toxic

5-50  mg/kg

Q. What do you mean by very toxic

51-500 mg/kg

Q. What do you mean by moderately toxic

501 mg/kg to 5 g/kg

Q. What do you mean by slightly toxic

5.1 g/kg to 15 g/kg

Q. What do you mean by practically non-toxic

More than 15 g/kg

Q. What is acute toxicosis

refers to effects during the first 24hr period

Q. What is subchronic toxicosis

effects produced by repeated exposure (<3months)

Q. What is chronic toxicosis

effects produced by prolonged exposure (>3months)

Q. What is LD?

lethal dose

Q. What is LD (LO)?

 lethal dose low; lowest dose that produced deaths

Q. What is LD (50)?

median lethal dose - calculated dose that is projected as being likely to cause death in half (50%) of the exposed animals of the species/strain/age/sex exposed.

Q. What is LC?

lethal concentration = lethal concentration of a toxicant in feed, water, soil or other 'matrix' to which the animals are exposed

Q. What is an addition/additive effect?

 When the combined effect of two compounds given together is equal in magnitude to sum of the effects of each compound given alone, the interaction is called addition and the effect produced is called additive effect.In this case no specific interactions occur.

  1 + 1 = 2

Q. What is synergism/synergistic effect?

The combined effect of the administration of two compounds may be greater than the sum of the two effects; this is called synergism.  The synergist piperonyl butoxide is added to some insecticides to greatly increase their toxicity to insects. 

Q. What is potentiation/potentiative effect?

When one compound having no effect of its own increases the effect of another compound the interaction is called potentiation and the effect produced is called potentiative effect. For example, a dose of a compound A is toxic to animals in vivo. Another chemical B is not toxic when given at doses several orders of magnitude higher but when the two are given together the toxic response is greater than that of the given dose of A alone. This means the compound B has a potentiative effect on compound A. This is known as potentiation.

For example:  1+ 1 = more than two

Q. What is the difference between synergism and potentiation?

The difference between the two concepts is that synergism is the interaction of two or more substances, while potentiation is about a singular substance and how it may act when in a synergy relationship.

Q. What is the difference between toxicity and toxicosis?

Toxicity is the relative potency of a toxicant - usually compared on a mg/kg basis. Toxicosis is a pathologic condition that results from exposure to a toxicant.

Q. What is the difference between dose and dosage?

Dose is the total amount of toxicant received by the animal and animal dosage is the amount of toxicant per unit of animal weight.

Q. What is the difference between quantal response and graded response?

A quantal response (population response) is a binary response, the effect happens or it does not happen i.e. all or none response. A graded response (individual response) is where the toxic effects become more severe as the dose increases.

Q. What is the difference between LD50 and therapeutic ratio?

LD50 is the dose likely to cause death in 50% of a given species/age/sex group under specified conditions. The therapeutic ratio is the ratio of LD50 to ED50 (units are %).

Q. What are the timeframes associated with acute, sub-chronic and chronic exposures?

Within 24 hrs:             acute toxicity

Within 30 days or less:            sub-acute toxicity.

within 1 to 3 months:               sub-chronic toxicity.

More than 3 months:               chronic

Q. Compare the different routes of toxicant exposure and their toxicant concentration.

IV has the highest concentration, followed by inhalation, then oral and dermal, which have similar concentrations.

Q. Name five toxicity factors associated with the toxicant.

1. Solubility

2. Polarity
3. Vehicle

4. Formulation effects

5. Chemical interactions

Q. Name eight factors associated with the environment that affect toxicity

1. season

2. temperature
3. light factors

4. housing
5. constructions

6. heating systems

7. air circulation
8. bedding

Q. What type of biotransformation happens in Phase I?

oxidation

reduction

hydrolysis

Q. What type of biotransformation happens in Phase II?

Conjugation with endogenous molecules

Q. Name five things that influence biotransformation?

1. Parenchymal organ disease

 2. Toxicant localization in tissues with little PI/PII activity

3. Age and metabolic activity 

4. Species-specific variation and individual variation

5. Gender and hormone differences

Toxicokinetics

Q. Describe First Order elimination Kinetics? How is this different to zero order kinetics?
https://lifeinthefastlane.com/first-order-and-zero-order-kinetics-pharmacology-bscc/

First order: First order reactions are the most common. These reactions occur when a constant proportion of the drug/toxicant is eliminated per unit time. Rate of elimination is proportional to the amount of drug/toxicant in the body. The higher the concentration, the greater the amount of drug/toxicant eliminated per unit time. For every half-life that passes the drug/toxicant concentration is halved (t1/2=0.693). For example, a drug/toxicant concentration of 100 and a half-life of one hour will reduce to 50 in the first hour, 25 in the second hour and 12.5 in the 3rd hour and so on. Most drugs/toxicant are eliminated this way. Elimination mechanisms are NOT saturable. 10 half-lives will virtually eliminate all the drug/ toxicant from the body.

Zero order: Zero order is a saturated process proceeding at maximum amount the body can handle per unit time. Reaction rate is independent of amount of drug/toxicant in the body. Kinetics may change to first order after process is no longer saturated. In this case a constant amount of drug/toxicant is eliminated per unit time. For example, 10mg of a drug may be eliminated per hour, this rate of elimination is constant and is independent of the total drug/toxicant concentration in the plasma. These reactions (zero order kinetics) are rare. Elimination mechanisms are saturable. Examples of zero order elimination include ethanol, phenytoin and salicylates (at high doses).

                                                                                                                       To be cont’d

FURTHER READING

Gupta PK (2018) Illustrative Toxicology with Question bank. 1st Edition. Elsevier, USA

Gupta PK (2016) Fundamentals of Toxicology: Essential concepts and applications. 1st Edition. ISBN-9780128054260, pp 438, BSP/Elsevier, USA

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

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

Gupta PK (2016) Essential Concepts in Toxicology. Published by PharmaMed Press (A unit of BSP Books Pvt. Ltd), Hyderabad, India pp 362.

Gupta PK (2010) Modern Toxicology, Basis of organ and reproduction toxicity. Vol 1. Published by Pharma  Med Press (A unit of BSP Books Pvt. Ltd). Hyderabad, India pp 1-460.

Gupta PK (2010) Modern Toxicology, Adverse effects of xenobiotics. Vol 2, Published by PharmaMed Press (A unit of BSP Books Pvt. Ltd). Hyderabad, India pp 1-460.

Gupta PK (2010) Modern Toxicology, Immuno and clinicsal toxicology Vol 3. Published by PharmaMed Press (A unit of BSP Books Pvt. Ltd). Hyderabad, India pp 1-340.