evaluation of certain food additives - libdoc.who.int - World Health ...

In a two-generation study of reproductive toxicity in rats, adults receiving
lycopene at a dietary dose of up to 500 mg/kg bw per day showed no evidence
of toxicity. The discoloured faeces and staining of fur/skin/fat/abdominal organs
observed were attributed to the presence of lycopene in the diet. Mating
performance, fertility, and survival and growth of the pups were not affected
by treatment with lycopene. The NOAELs for parental, reproductive and
offspring toxicity were all 500 mg/kg bw per day, the highest dose tested.
In studies of developmental toxicity in rats and rabbits, no teratogenicity was
observed. Similarly, there were no treatment-related increases in the overall
number of external, visceral or skeletal abnormalities and variations. In all
developmental studies, the dams showed discoloured faeces, and the contents
of the gastrointestinal tract appeared discoloured in the gavage studies. Given
the absence of any adverse toxicological findings, the NOAELs for maternal
and developmental toxicity were at the highest tested doses in both rats and
rabbits, 1000 and 400 mg/kg bw per day, respectively.
Studies in humans, although not specifically designed to assess the safety of
lycopene, revealed no adverse effects after administration of dietary lycopene.
There are, however, case reports of skin discoloration (lycopenodermia)
and/or gastrointestinal discomfort after prolonged high intakes of
lycopene-rich food and/or supplements, those effects being reversible upon
cessation of lycopene ingestion.
Assessment of dietary exposure
Dietary exposure to lycopene naturally present in food is likely to be up to
10 mg/day in adults. Lycopene used as a food colour can be derived from a
number of different sources, such as synthetic lycopene, lycopene derived
from Blakeslea trispora and lycopene extract from tomato. However, it is
likely that lycopene from these sources will be substituted for one another as
food colours when used in accordance with Good Manufacturing Practice.
Therefore, the dietary exposure to lycopene from all these sources will be
similar. Based on the proposed use levels, dietary exposure to lycopene added
as a food colour is estimated to be up to 5 times higher than the upper end of
the range of the background exposure, 10 mg/day.
Evaluation
Lycopene is a normal constituent of the human diet, and the background dietary
exposure to lycopene from vegetables and fruits is up to 10 mg/person
per day. The available data indicate that dietary lycopene is generally well
tolerated in humans. After prolonged high intake of lycopene-rich food and/
or supplements, the effects were limited to skin discoloration and/or gastrointestinal
discomfort. The Committee reconsidered the available toxicological
data, including a new 28-day study, together with the dietary exposure
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