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the various endpoints of developmental and reproductive toxicity.
Funding aspects:
• A long-term (5-10 year) developmental funding process is needed, as e.g., the
SEURAT-1 project for repeated dose toxicity
• Joint public-private partnerships between the private sector NGOs and international
governments are recommended, building on the positive experience from the SEURAT-1
project
• An integrated cluster of projects covering essential pathways is recommended.
Building public confidence in a new safety evaluation paradigm to:
• Prove that the new approach provides better protection for humans and/or the
general public than the current approach
• Demonstrate that the transparency of the new approach in contrast to the current
‘black box’ concept
• Ensure that uncertainties are clearly understood.
Supplemental Background Information
Specific principles of reproductive toxicology
Mammalian reproduction is characterised by a rather complex reproductive cycle, the
essential steps of which are depicted in Figure 2. Reproductive toxicology covers a
wide spectrum of toxic effects at all stages of the reproductive cycle, starting with
female and male fertility, prenatal and postnatal development, and culminating in late
manifestations that can only be detected in the next generation. Thus, in contrast to
other fields of toxicology, reversible and irreversible effects of exposure to toxicants may
occur, not only in individuals that were exposed, but also in their offspring.
Risk assessment is particularly challenging in reproductive toxicology, due to the
complexity and unusually long timeframe/duration of the reproductive cycle, which
covers at least two generations. To assess the potential of chemicals to interfere with
reproduction, animal-based test methods must cover these essential steps (Figure 2):
a) growth and maturation of sperm and oocyte;
b) fertilisation, e.g., fusion of oocyte and sperm, resulting in a complete, diploid set
of chromosomes;
c) normal cleavage divisions, implantation, intrauterine development, birth, and
postnatal development throughout the period of lactation; and
d) normal development of the offspring to fertile adult animals, which are able to
AXLR8-2 WORKSHOP REPORT
Progress Report 2011 & AXLR8-2 Workshop Report
341