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- Practical Guide -
Page 140 of 153
3.
TOXICOLOGICAL DATA, QUANTITATIVE RESTRICTIONS
The conclusions from the toxicological data depend, first of all, on whether or not the
set of mutagenicity tests indicates genotoxicity.
3.1. For non-genotoxic substances, usually a dose causing no observed adverse effects in
laboratory animals (NOAEL) can be determined. If the NOAEL has already been
evaluated by the SCF or JECFA, usually no reassessment is required. For further
details, see "SCF Guidelines". For other substances a "tolerable daily intake" (TDI) for
man is calculated, expressed in mg/kg body weight (b.w.) and applying a safety factor,
which accounts for:
a)
Possible differences between animals and man in their reaction to chemicals;
b)
Possible differences in sensitivity to chemicals between individuals of a
population;
c)
Uncertainties in assessing the NOAEL in animals;
d)
Uncertainties due to difficulties in carrying out adequate monitoring of human
populations to detect unexpected adverse effects in man
If the toxicity data (e.g. referring to the "essential core set of tests" of the "SCF Guidelines")
is considered adequate, usually a safety factor of 100 is applied.
3.2 Substances having a reduced technical dossier
3.2.1 If migration (M) is between 0.05 and 5 mg/kg food or food simulant, a "reduced
dossier" is sufficient (see "SCF Guidelines"), and the SCF proposes a restriction less or
equal to 5 mg/kg.
3.2.2 If migration remains below 0.05 mg/kg food or food simulant, a "reduced dossier"
containing at least three specified mutagenicity tests may be supplied, and the SCF will
propose a restriction below or equal to 0.05 mg/kg of food or food simulant.
3.3. Genotoxic substances or substances showing other high toxicity (e.g. sensitizers), for
which the present scientific knowledge does not allow the establishment of a NOAEL,
are usually classified in lists 4 or 5.