Toxicology of Industrial Compounds

366 CONTROVERSIAL ISSUES IN SAFETY ASSESSMENT
reduction or impairment of fertility observed at 800 mg kg −1 day −1 in
anappropriate developmental or reproductive test without parental
toxicity would lead to classification into the respective category 3 or
possibly category 2, even if a NOEL was found at 400 mg kg −1 day −1 .
This certainly is not appropriate when considering the reversibility
and severity of the effects and the differences in the NOELs and
LOELs of one order of magnitude.
Risk assessment
The general strategy in risk assessment of chemicals with threshold effects
is to use ‘assessment’ factors (‘uncertainty’ or ‘safety’ factors) (AF) for
setting appropriate exposure limits. This concept was originally introduced
by the WHO to establish ADI values (acceptable daily intake) for pesticide
residues in food. Here generally a ‘safety’ factor of 100 is applied to the
NOEL of a chronic experiment; higher or lower factors might be used for
specific effects or experimental conditions.
This basic approach can be generalized from consumer exposure to
pesticide residues in food to other chemicals and exposure scenarios. The
main problem then will be the selection of an appropriate AF. First of all,
there are some general considerations to be taken into account:
– Should AFs for the workforce and the general population differ because
of the age characteristics and the general health status of workers?
– Should different AFs be selected for chemicals and pesticides, taking into
account that pesticides are specifically tailored for biological activity?
– What are suitable AFs for route to route extrapolations if the
experimental exposure does not correspond to that of humans? Thereby
metabolic firstpass effects in the liver and different efficacies of the
adsorption barriers of skin, lung and the intestines have to be taken into
account.
– What is the appropriate dose parameter, mg kg −1 body weight, mg m −2
surface area or concentration?
– What are suitable AFs for developmental effects which may occur in
principle after a single exposure and may lead to irreversible lifetime
impairment?
– Are specific AFs necessary for toxic effects on the reproductive organs as
compared to toxic effects on other organ systems?
Apart from these general considerations there are also specific criteria
decisive for the selection of AFs depending on each single chemical, its
total data base and the experimental details. Very often the final AF is
obtained by additional default factors which are to account for