Safety evaluation of certain food additives - ipcs inchem

560 MISCELLANEOUS NITROGEN-CONTAINING SUBSTANCES (addendum)
gavage (National Toxicology Program, 1982) is appropriate because they are
all alkyl isothiocyanates and will be metabolized via similar metabolic pathways.
The NOEL of 12 mg/kg bw per day for allyl isothiocyanate (No. 1560) provides
margins of safety in the range of 5400–24 000 000 in relation to their estimated
levels of intake.
For 4-(methylthio)butyl isothiocyanate (No. 1892), 5-(methylthio)pentyl
isothiocyanate (No. 1896) and 6-(methylthio)hexyl isothiocyanate (No. 1897),
the NOEL of 30 mg/kg bw per day for the structurally related flavouring agent
3-(methylthio)propyl isothiocyanate (No. 1564) from an 84-day feeding study in
rats (Harper et al., 1961) is appropriate because they are all linear mercaptoisothiocyanates
and will be metabolized via similar metabolic pathways. The
NOEL of 30 mg/kg bw per day for 3-(methylthio)propyl isothiocyanate (No.
1564) provides margins of safety in the range of 600 000–15 000 000 in relation
to their estimated levels of intake.
Table 1 summarizes the evaluations of the 14 miscellaneous nitrogencontaining
substances in this group.
1.5 Consideration of combined intakes from use as flavouring agents
In the unlikely event that the flavouring agents in a homologous series of
linear saturated isothiocyanates in structural classes II and III, of which the highest
intakes correspond to Nos 1561, 1884, 1885, 1891 and 1895 in Europe and Japan,
were to be consumed concurrently on a daily basis, the estimated combined intakes
of 2 and 0.89 μg/person per day in Europe and Japan, respectively, would not
exceed the thresholds of concern (i.e. 540 μg/person per day for class II and
90 μg/person per day for class III).
In the unlikely event that the flavouring agents in a homologous series of
branched-chain saturated isothiocyanates in structural class II, of which the highest
intakes correspond to Nos 1886, 1887, 1888 and 1890 in Japan, were to be
consumed concurrently on a daily basis, the estimated combined intake of 16 μg/
person per day in Japan would not exceed the threshold of concern (i.e. 540 μg/
person per day for class II).
In the unlikely event that the flavouring agents in a homologous series of
linear saturated mercapto-isothiocyanates in structural class II, of which the highest
intakes correspond to Nos 1564, 1892, 1896 and 1897 in Europe, the USA and
Japan, were to be consumed concurrently on a daily basis, the estimated combined
intakes of 13, 52 and 3.2 μg/person per day in Europe, the USA and Japan,
respectively, would not exceed the threshold of concern (i.e. 540 μg/person per day
for class II).
In the unlikely event that the flavouring agents in a homologous series of
linear unsaturated isothiocyanates in structural class II, of which the highest intakes
correspond to Nos 1560, 1889, 1893 and 1894 in Europe, the USA and Japan, were
to be consumed concurrently on a daily basis, the estimated combined intakes
would be 1502, 133 and 222 μg/person per day in Europe, the USA and Japan,
respectively. The estimated combined intake would exceed the threshold of concern
in Europe (i.e. 540 μg/person per day for class II). The intake in Europe, however,
is due mainly to allyl isothiocyanate (No. 1560). Allyl isothiocyanate has a NOEL of