Toxicology and Drug Safety

Course content

The course gives an overview of fundamentals in human toxicology and drug safety. Topics encompass toxicokinetics and toxicodynamics for major groups of xenobiotics mainly drugs, and mechanisms by which xenobiotics exert their toxic action. The course also provides an overview as to how absorption, distribution, metabolism and excretion affect the toxicology and safety of drugs and provides a thorough insight into the mechanisms of drug metabolism. Furthermore the course will give an understanding of target organ toxicity, including toxic effects on liver and kidneys, the skin, the brain and the respiratory system. System toxicology such as effects on immune systems and hormone systems, genotoxicity, mutagenicity, teratogenicity and cancer development are also important elements of the course. The course will also discuss in detail how to quantify a dose or an exposure of a chemical and be able to predict most important exposure routes or pathways.

Safety assessment in drug development and regulatory safety aspects of drug development will be addressed including pharmacovigilance measures preapproval and post-marketing. Occupational toxicology will focus on exposure to chemicals during drug development and production. This includes the calculation of occupational exposure limits.

The overall aim of this course is to prepare the students to be able to perform simple benefit-risk assessments in drug regulatory decision-making and risk assessments scenarios for environmental and occupational health hazards and to evaluate potential hazards of a given xenobiotic. 

Education

MSc Programme in Pharmacy or Pharmaceutical Sciences (Danish programmes cand.pharm and cand.scient.pharm) - compulsory

MSc Programme in Medicinal Chemistry - elective

MSc Programme in Pharmaceutical Sciences (English programme) - elective

 

Learning outcome

Objective

The main objectives of the course is to introduce fundamentals and key methods in human toxicology and drug safety, and to provide an overview of different approaches for acquiring data that may be applied in risk assessment and benefit-risk evaluation of pharmaceuticals to humans. The course consists of a number of lectures and a written assignment. The course is recommended for students who upon completion of their studies will be employed in sectors dealing with pharmaceuticals, drug development, preclinical and clinical testing and assessment, and health risks including public inspection, public health, drug agencies, environmental consulting, medical industry and the bioprocessing industries.

 

Upon completion of the course, the student will be able to:
 

Knowledge

  • understand the principles of xenobiotic uptake, distribution, metabolism and excretion
  • describe toxicological mode of actions for the most important groups of chemical substances to humans and environmental species.
  • define the most vulnerable target organ(s) or organism(s) for most important group of xenobiotics.
  • demonstrate knowledge on drug safety and toxicology, and extrapolation from animal to human.
  • demonstrate knowledge on regulatory aspects of drug safety
  • understand the use of physico-chemical parameters of compounds to predict toxicity, bioaccumulation and biomagnification.
  • assess both acute and chronical toxicity data and evaluate different types of dose-response relationships including effects of mixtures of compounds with similar mode of action.
  • Identify level of exposure of a chemical and be able to predict the most important exposure routes to humans and environment.
  • understand the principles of pharmacovigilance and its application in drug development and postmarketing.
  • suggest how to diminish an exposure of chemical in both human, experimental animals and environment.

 

Skills

  • conduct an exposure analysis of a drug.
  • utilise relevant software for dose-response relationships and problem solving (e.g. EPI-Win, Chem-Draw, Excel, R).
  • design simple in vitro dose-response toxicological tests.
  • estimate EC50-values, NOAELs and LOAELs for a given drug exposure based on dose-response curves.
  • report scientific results and human drug exposure scenarios as a case report.

 

Competencies

  • integrate principles from chemistry, physics, biology, biochemistry and physiology to solve simple toxicological questions.
  • apply principles of 3R (Replacement, Reduction, Refinement) to toxicological testing scenarios.
  • apply simplified assumptions and estimate model and design parameters in the face of biological variability and uncertainty in measurement and prediction.
  • Apply risk-benefit analysis and risk-assessment to human drug exposure scenarios.

 

Lectures, theoretical exercises, and a written assignment will be the main form of teaching. Lectures are based on textbooks, lecture notes and some scientific papers. The topics of the theoretical exercises run in parallel with the topics treated in the lectures.
The written assignment (a case with 2 levels) will be performed in groups of 3-4 students that will work together to produce a case on a given drug scenario. The purpose is to train the student to collect and evaluate peer-review scientific data on a given subject within drug toxicology and safety, and to perform a benefit-risk evaluation. Results are reported as a case report.
24 blocks of 4 hours each.

  • John Timbrell 'Principles of Biochemical Toxicology', 4rd edition, Taylor & september 2009
  • Different notes and scientific papers provided on the course homepage (English)

The course presumes knowledge at university bachelor level of 5 ECTS -credits in human or animal physiology, in biochemistry, in organic chemistry and in inorganic chemistry. Thus a total of minimum 20 ECTS credits. In addition, knowledge of biology and microbiology will be an advantage.

Continuous feedback during the course of the semester
Feedback by final exam (In addition to the grade)
ECTS
See exam description
Type of assessment
Written assignment
The written assignment consists of a case study in 2 sections and is performed in groups of 3 students. The two sections are weighted equal.
Aid
All aids allowed
Marking scale
7-point grading scale
Censorship form
External censorship
Criteria for exam assessment

To achieve the grade 12 the student must be able to:

Knowledge

  • describe toxicological mode of actions for most important groups of chemical substances to humans and environmental species.
  • define the most vulnerable target organ(s) or organism(s) for most important group of xenobiotics.
  • demonstrate knowledge on safety toxicology, and extrapolation from animal to human.
  • understand the use of physico-chemical parameters of compounds to predict toxicity, bioaccumulation and biomagnification
  • assess both acute and chronical toxicity data and evaluate different types of dose-response relationships including effects of mixtures of compounds with similar mode of action.
  • quantify a dose or an exposure of a chemical and be able to predict the most important exposure routes to humans and environment and exposure due to occupation.
  • suggest how to diminish an exposure of chemical in both human, environmental and occupational toxicology (practical management).
  • classify chemicals and xenobiotics (Tx, T, Xn, C and Xi).

 

Skills

  • transfer math concepts to solve 1st-order linear differential-integral equations, manipulate log relationships, convert between dimensional systems of units.
  • utilise relevant software for dose-responds relationships and problem solving(e.g. EPI-Win, Chem-Draw, Excel, R).
  • have knowledge on simple in-vitro toxicological tests and models.
  • report scientific results as a risk assessment report.

 

Competencies

  • integrate principles from chemistry, physics, biology, biochemistry and physiology with mass and energy balances to develop and solve simple toxicological questions.
  • apply simplified assumptions and estimate model and design parameters in the face ofbiological variability and uncertainty in measurement and prediction.
ECTS
See exam description
Type of assessment
Written examination, 2 timer under invigilation
Multiple choice exam.
Aid
Written aids allowed

There is access to the following at the exam on Peter Bangs Vej:

  • Office (Word, Excel, Onenote and Powerpoint)
  • IO2 – the digital pen
  • Panoramic Viewer
  • Paint
  • Calculator – Windows' own
  • R – Statistical programme
  • ITX MC – multiple choice programme
  • MathType - formel programme
  • Mable
  • Adobe reader
  • USB access – for usb stick with notes etc.

 

During the exam students are allowed to bring approved pocket calculator, molecular model building set and USB stick.

Marking scale
7-point grading scale
Censorship form
No external censorship
Criteria for exam assessment

To achieve the grade 12 the student must be able to:

Knowledge

  • describe toxicological mode of actions for most important groups of chemical substances to humans and environmental species.
  • define the most vulnerable target organ(s) or organism(s) for most important group of xenobiotics.
  • demonstrate knowledge on safety toxicology, and extrapolation from animal to human.
  • understand the use of physico-chemical parameters of compounds to predict toxicity, bioaccumulation and biomagnification
  • assess both acute and chronical toxicity data and evaluate different types of dose-response relationships including effects of mixtures of compounds with similar mode of action.
  • quantify a dose or an exposure of a chemical and be able to predict the most important exposure routes to humans and environment and exposure due to occupation.
  • suggest how to diminish an exposure of chemical in both human, environmental and occupational toxicology (practical management).
  • classify chemicals and xenobiotics (Tx, T, Xn, C and Xi).

 

Skills

  • transfer math concepts to solve 1st-order linear differential-integral equations, manipulate log relationships, convert between dimensional systems of units.
  • utilise relevant software for dose-responds relationships and problem solving(e.g. EPI-Win, Chem-Draw, Excel, R).
  • have knowledge on simple in-vitro human toxicological tests and models.
  • report scientific results as a risk assessment report.

 

Competencies

  • integrate principles from chemistry, physics, biology, biochemistry and physiology with mass and energy balances to develop and solve simple toxicological questions.
  • apply simplified assumptions and estimate model and design parameters in the face ofbiological variability and uncertainty in measurement and prediction.

Single subject courses (day)

  • Category
  • Hours
  • Lectures
  • 60
  • Exercises
  • 12
  • Guidance
  • 8
  • Study Groups
  • 16
  • Preparation
  • 108
  • Exam
  • 2
  • English
  • 206