Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 549

and then applies a factor to derive an exposure which has a high likelihood that no
effect will occur in the general human population.
These exposure limits are derived by first determining the No Observed Adverse
Effect Level (NOAEL) or, if the NOAEL cannot be determined, the Lowest
Observed Adverse Effect Level (LOAEL) and dividing the value by factors to
account for:

• interspecies differences (extrapolating from animals to humans);

• intraspecies differences (differing sensitivities between individuals);

•

the severity of the adverse effect; and

•

the quantity and quality of the scientific data.

Traditionally, safety factors for intraspecies and interspecies differences have
each been assigned values of ten, and the other two have been assigned values
between 1 and 10. An additional factor of ten is sometimes used if the NOAEL was
not established in the study. The individual factors are then multiplied to determine
an overall safety factor by which the NOAEL is divided to give the ADI, PTWI,
TDIorRfD.
Historically, the most common overall factor used by a number of regulatory
bodies is 100 if a large toxicological database has been assessed, although the over-
all factor can range from 10 to 10,000. From the data available on humans and
experimental animals, it appears that interspecies and intraspecies differences are in
general less than 10, hence the often-used overall safety factor of 100 for these two
factors is conservative and adequately protective of public health (Johannsen 1990 ;
Renwick and Walker 1993 ).
The decision on the magnitude of factors to use is predominantly based on expert
or informed judgement. Whilst this approach to selecting the number and magnitude
of the safety factors appears to be arbitrary, current knowledge of the biological
processes which cause inter- and intraspecies variation (e.g., metabolic and other
pharmacokinetic rate differences) support the choice of safety factors.
REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals)
provides a European Union legislative framework for chemicals. Both REACH and
WHO are producing documents on factors derived from empiric databases and
substance - specific adjustment factors.

12.5.4 Non-Threshold Approaches

These approaches do not recognise the possibility of a threshold effect and are
appropriate for radiation and for some genotoxic carcinogens. It is, as a science
policy decision, applied to all carcinogens by the US EPA.
Non-threshold models assume linearity between the lowest experimentally
derived dose and the zero dose. This implies that there is a calculable probability
of an adverse effect (risk) no matter how small the dose.