Safety evaluation of certain food additives - ipcs inchem

PAPRIKA EXTRACT 89
biochemical parameters were assessed. At the end of the chronic study (52 weeks),
10 animals per group were killed, and the balance of surviving animals were killed
at the end of the 104-week carcinogenicity study. All animals were subjected to
complete pathological evaluation. There were no effects in either study on survival
rates, clinical signs of toxicity, or food consumption and body weight. Likewise, there
were no effects on haematological parameters, serum biochemical measures or
organ weights. There also was no evidence of pathological changes, with the
exception of an increased incidence of hepatocellular vacuolation in the 5% males,
a finding the authors noted was not adverse. Likewise, there was no effect of
treatment on the pattern or incidence of tumours.
2.3.3 Genotoxicity
Numerous studies have been performed with extracts of chilli peppers
and with samples of capsaicin of different levels of purity, and the findings have
been mixed, inconsistent and often contradictory. For example, both capsaicin
and extracts were reported to show positive effects in bacterial assays (Toth et al.,
1984; Damhoeri et al., 1985; Nagabhushan & Bhide, 1985; Venkat et al., 1995), with
inconsistent results in the presence or absence of S9 mix for metabolic activation,
whereas both capsaicin (Damhoeri et al., 1985) and extracts (Buchanan et al.,
1981) were reported to have no effects in other bacterial tests. Both positive
(Nagabhushan & Bhide, 1985; Lawson & Gannett, 1989) and negative
(Nagabhushan & Bhide, 1985) results have been reported in assays using Chinese
hamster V79 cells. Capsaicin was found to induce deoxyribonucleic acid (DNA)
damage in cultured neuroblastoma cells at doses that were also shown to be
cytotoxic, as monitored by inhibition of protein synthesis (Richeux et al., 1999).
Studies conducted in mice have shown that pepper extract can induce micronuclei
in bone marrow, but that the capsaicin-containing fraction does not (Villasenor & de
Ocampo, 1994; Villasenor et al., 1995). In contrast, Arceo et al. (1995) reported that
capsaicin induces micronuclei in the mouse and also sister chromatid exchange
only at the highest dose, whereas capsaicin administered intraperitoneally to mice
did not induce dominant lethal mutation (Muralidhara & Narasimhamurthy, 1988).
Since the time of these earlier studies and of the review in 2002 by the
Scientific Committee on Food, more definitive studies have been performed using
pure capsaicin. In a battery of studies, Chanda et al. (2004) found that pure
capsaicin induced a weak response after 4 h of treatment in the range of toxic
concentrations in the mouse lymphoma assay but was non-mutagenic when
treatment was extended to 24 h, and they commented that the criteria for positive
results from this assay remain controversial. Results were uniformly negative using
pure capsaicin in the Ames test and in human lymphocytes assayed for
chromosomal aberrations (Chanda et al., 2004; Proudlock et al., 2004). Finally, in
whole animal studies, bone marrow micronuclei were not induced either in the
mouse (Chanda et al., 2004) or in the rat (Proudlock et al., 2004).
Taken as a whole, it can be concluded that pure capsaicin is non-genotoxic
in standard genotoxicity assays and has no in vivo genotoxic potential.