Combined Actions and Interactions of Chemicals in Mixtures

7.4 Reproductive toxicity
Prepared by Otto Meyer, Alireza Hossaini and Majken Dalgaard
7.4.1 Introduction
Reproduction is the term used to describe the biological processes, which ensures
the continuation of species. Through this process the existing genetic material is
passed on to the next generation. The reproductive cycle does not consist simply of
conception, pregnancy and birth. It actually begins with the formation of the
primitive germ cells in the parents at the embryo-foetal stage and does not end until
sexual maturity has been reached. A disturbance of the reproductive cycle can,
depending upon type or timing, prevent or inhibit reproduction or result in
developmental defects in the offspring. Developmental toxicants can affect growth,
development or acquisition of normal organ function between conception and
puberty. Exposure to such compounds may lead to death (in utero or postnatal),
structural defects, growth retardation, and functional deficits or childhood cancer.
In developmental and reproductive toxicology the following potential effects
caused by exposure to chemical mixtures have been considered:
• Impairment of male and female reproductive functions or capacity, i.e.
adverse effects on libido, sexual behaviour, aspects of spermatogenesis or
oogenesis, hormonal activities or physiological responses which would
interfere with the capacity to fertilise, with the fertilisation itself or the
development of the fertilised ovum up to and including implantation.
• Induction of harmful effects on the progeny in the widest sense that is
effects interfering with the normal development, both before and after birth
up to puberty. Both morphological malformation(s) and functional
disturbances (e.g. hormonal, neurological) are included.
The above-mentioned developmental effects are considered to be non-inheritable
effects. This should be taken with some reservation, as the data very often do not
offer the possibility to distinguish or identify the cause(s) of the developmental
effect. Thus, for 65-70% of developmental defects in man the causes of the
pathogenesis are not known.
Many different experimental methods are in use for the assessment of reproductive
toxicity of chemicals (Table 7.4.1.1). When the results of testing single compounds
are used in the risk assessment of human exposure to chemicals in complex
mixtures there are a number points to consider. These points include the inherent
differences in the experimental conditions e.g. laboratory animal species, strain or
stock, diet and dosing. In addition, time-effect relationships like the relative timecourses
of action of the single agents and the time courses of action of the agents
relative to the timing of developmental events occurring during gestation must also
be considered when interpreting interactive effect on e.g. the development.
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