Programme: Health risk assessment of reproductive toxicity and endocrine disruptors
November 7-11, 2016
IMM Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, Stockholm, Floor 2, Bergendorff room
Course leaders: Johanna Zilliacus and Annika Hanberg
Monday Nov 7
9.00-9.30
Welcome and introduction to
the course (JZ, AH)
Tuesday Nov 8
9.00-9.45
Group work
Wednesday Nov 9
9.00-9.45
Maternal toxicity (AH)
9.30-10.30
Introduction of participants
10.30-11.00
Coffee break
9.45-10.15
Coffee break
10.15-11.00
Toxicity testing of
reproductive toxicity and
endocrine disruption (AH)
11.15-12.00
Endocrine disruptors and
health – The use of registers
and biobanks in
epidemiological studies (LR)
12.00-13.00
Lunch
13.00-13.45
Adversity (AH)
9.45-10.15
Coffee break
10.15-11.00
Maternal toxicity (AH)
13.45-14.15
Coffee break
14.15-15.00
Adverse outcome pathways
(AB)
15.15-15.45
Criteria for endocrine
disruptors (JZ)
11.00-12.00
Introduction to risk
assessment of reproductive
toxicity and endocrine
disruption (AH)
12.00-13.00
Lunch
13.00-13.45
Developmental biology and
endocrinology (JZ)
15.45-17.00
Group work
Thursday Nov 10
9.00-9.45
Identification and assessment
of developmental
neurotoxicity (SS)
9.45-10.15
Coffee break
10.15-11.00
Identification and assessment
of developmental
neurotoxicity (SS)
11.15-12.00
Weight of evidence (AB)
Friday Nov 11
9.00-9.45
Presentation and discussion of
group work
12.00-13.00
Lunch
13.00-14.15
Regulatory aspects of
reproductive toxicity and
endocrine disruption (IMO)
12.00-13.00
Lunch
13.00-13.45
Group work
Take home exam handed in at
17.00
13.45-14.15
Coffee break
14.15-15.00
Group work
14.15-14.45
Coffee break
14.45-15.45
Dose-response relationships
(JZ)
13.45-14.15
Coffee break
14.15-17.00
Group work
14.45-16.15
For Master’s students: Web
lecture on ToxCast by Rusty
Thomas, EPA (optional for
other participants)
16.15-17.00
Group work
15.45-17.00
Group work
11.15-12.00
In vitro tests for reproductive
toxicity and endocrine
disruption (JZ)
9.45-10.15
Coffee break
10.15-12.30
Presentation and discussion of
group work
12.30-13.00
Course ending
Teachers:
AB – Anna Beronius, IMM, KI
AH – Annika Hanberg, IMM, KI
IMO – Ing-Marie Olsson, Swedish Chemicals Agency
JZ – Johanna Zilliacus, IMM, KI
LR – Lars Rylander, Lund University
SS – Stefan Spulber, Dept of Neuroscience, KI
Course information
Purpose of the course:
The purpose of the course is to give the student knowledge and understanding of how to assess health risks of
chemical substances that cause reproductive toxicity including endocrine disruptors.
Learning outcomes:
After the completion of the course the student shall be able to:
 describe the principles for health risk assessment of reproductive toxicity
 explain how different types of data from in vivo, epidemiological and in vitro studies are used for health
risk assessment of reproductive toxicity
 identify and discuss complexities in health risk assessment of reproductive toxicity
 identify and discuss complexities in health risk assessment of endocrine disruptors
Content of the course:
Reproductive toxicity describes toxic effects of a chemical substance on the reproductive ability as well as on
the development of the offspring. Health risk assessment of reproductive toxicity addresses the procedures to
identify and characterise the reproductive toxicity with the aim to derive health based guidance values for safe
levels of the chemical substances. Endocrine disruptors are substances that alter the endocrine system and are a
special concern for risk assessment of reproductive toxicity.
The course introduces the concepts in reproductive toxicity as well as of endocrine disruptors. Methods for
identification and assessment of reproductive toxicity are described and discussed. Regulatory aspects of
reproductive toxicity and endocrine disruption will be covered. Attention will be paid to evaluation of different
type of data. Specific challenges in risk assessment of reproductive toxicity and of endocrine disruptors such as
nonmonotone dose response curves, low-dose effects and epigenetic mechanisms will be discussed.
Content of individual teaching and learning activities:
Introduction to risk assessment of reproductive toxicity and endocrine disruption
 Introduction to risk assessment
 What is reproductive toxicity
 What is endocrine disruption
Developmental biology and endocrinology
 Developmental biology
 Endocrinology
 Epigenetics
Adverse outcome pathways (AOPs)
 Introduction to AOPs
 MIE, KE, AO, KER
 AOP wiki
Criteria for endocrine disruptors
 Draft scientific criteria for endocrine disruptors
 Challenges to apply criteria
Toxicity testing of reproductive toxicity and endocrine disruption
 Guidelines
 Study design
 Assessment and interpretation of data
Endocrine disruptors and health – the use of registers and biobanks in epidemiological studies
 Design of epidemiological studies to identify endocrine disruption
 Assessment of the data
Adversity
 Adverse outcomes in reproductive toxicity
Maternal toxicity
 Maternal toxicity
 Discussion of papers on whether the effects observed in the offspring can be regarded as indirect
secondary effects due to maternal toxicity
In vitro tests for reproductive toxicity and endocrine disruption
 Available in vitro tests
 Role of in vitro tests
Regulatory aspects of reproductive toxicity and endocrine disruption
 Requirement in different relevant regulations CLP, REACH, Biocides, PPR
 Examples
Dose-response relationships
 Thresholds and linear dose-response relationships
 Non-monotonic dose-response relationships
 Low-doses
Identification and assessment of developmental neurotoxicity
 What is developmental neurotoxicity
 Tests for developmental neurotoxicity
 Assessment and interpretation of data
Weight of evidence
 Assessment of data
 Weight of evidence
Group work
 Analysis and discussion on approaches for risk assessment of reproductive toxicity and endocrine
disruption
 Oral presentation of group work
Take home exam
 Short answer questions on factual knowledge of important principles
 Essay questions on complexities in health risk assessment of reproductive toxicity and endocrine
disruptors