Safety evaluation of certain food additives - ipcs inchem

CALCIUM LIGNOSULFONATE (40–65) 35
supplements was for supplements containing vitamin E at 300 mg/day, calculated
by applying the relevant ratio of use for vitamin E to calcium lignosulfonate (40–65)
to the UL for vitamin E. However, the manufacturers predict that maximum dietary
exposure to calcium lignosulfonate (40–65) in multivitamin supplements could reach
400 mg/day or 7 mg/kg bw per day, assuming they contain all four vitamins, A, D,
E and K, and assuming a body weight of 60 kg. It is likely that potential dietary
exposures to calcium lignosulfonate (40–65) as a carrier for carotenoids or fatsoluble
vitamins were overestimated, as use is limited to only the powdered form of
the individual fat-soluble vitamin or carotenoid (50% of the total amount of
carotenoids produced, 35–50% of the total amount of fat-soluble vitamins
produced), not all these uses will be suitable for calcium lignosulfonate (40–65) as
a carrier and there may be alternative carriers available.
5. EVALUATION
In a metabolic study in rats, calcium lignosulfonate (40–65) was found to be
poorly absorbed from the gastrointestinal tract. However, owing to the limitations of
the study, it is difficult to determine the extent to which material of low molecular
weight may be absorbed.
The toxicity data on calcium lignosulfonate (40–65) consist of a 28-day and
a 90-day study of toxicity, negative results from a study of genotoxicity in vitro and
a study of developmental toxicity that showed no adverse effects in either dams or
fetuses. The NOEL for developmental toxicity in this study was 1000 mg/kg bw per
day, the highest dose tested. In the 28-day study, inflammation of the rectum was
observed, but this effect was not seen in the more extensive 90-day study. In the
90-day study, all the treated groups of animals displayed histiocytosis in the
mesenteric lymph nodes, and the incidence of this effect increased with increasing
dose. The histiocytosis seen in the mesenteric lymph nodes of rats treated with
calcium lignosulfonate (40–65) has been observed with other substances of high
molecular weight, such as polypentosan sulfate and copovidone (a copolymer of
vinylpyrrolidone and vinyl acetate). Long-term studies with these substances in rats
indicated that the histiocytosis does not progress and is not associated with
carcinogenesis.
On the basis of the available data, the Committee concluded that the
histiocytosis in the mesenteric lymph nodes of rats fed calcium lignosulfonate
(40–65) is of no toxicological consequence; thus, the NOEL in the 90-day study is
the target dose of 2000 mg/kg bw per day. The Committee therefore established an
acceptable daily intake (ADI) of 0–20 mg/kg bw based on the NOEL of 2000 mg/kg
bw per day from the 90-day study and application of a safety factor of 100. The 100fold
safety factor was considered by the Committee to be appropriate in the case of
calcium lignosulfonate (40–65), despite the absence of a long-term study, because
of its poor absorption, lack of toxicity in the 90-day study and lack of evidence for
developmental toxicity. In comparison with the ADI of 0–20 mg/kg bw, the maximum
potential dietary exposure to calcium lignosulfonate (40–65) was low and not
expected to exceed 7 mg/kg bw per day from use as a carrier of fat-soluble vitamins
and carotenoids in food and supplements.