EFSA Cannot Assess Safety of Calcium Lignosulphonate as a Vitamin and Carotenoid Carrier

Calcium lignosulphonate (40-65) is an amorphous yellow-brown to brown polymer derived from lignin, not having a well defined structural or molecular formula, with an average molecular weight between 40000 and 65000 g/mol.

18 Mar 2010 --- Following a request from the European Commission, the Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion on the safety of calcium lignosulphonate (40-65) when used as a carrier for vitamins and carotenoids intended to be added to foods for colouring and nutrient purposes.

According to the petitioner, the proposed name of calcium lignosulphonate (40-65) distinguishes the product from other available calcium lignosulphonates presenting lower degrees of lignin polymerisation and higher content of sugars. Lignosulphonates are used in a variety of food manufacturing applications including dispensing, binding, complexing and emulsifying.

Calcium lignosulphonate (40-65) is an amorphous yellow-brown to brown polymer derived from lignin, not having a well defined structural or molecular formula, with an average molecular weight between 40000 and 65000 g/mol.

In vitro and in vivo assays have shown that calcium lignosulphonate (40-65) is poorly absorbed by the oral route.

Calcium lignosulphonate (40-65) has been tested in in vitro genotoxicity, short-term, subchronic and developmental toxicity studies in accordance with recognised guidelines. No long-term or carcinogenicity studies were conducted with calcium lignosulphonate (40-65).

From the results obtained in vitro from one bacterial reverse mutation assay and one mammalian chromosomal aberration assay it can be concluded that there is no indication for a genotoxic potentialof calcium lignosulphonate (40-65). The Panel noted that a test for induction of gene mutations in mammalian cells in vitro, as recommended by the Guidance on submissions for food additive evaluations (SCF, 2001), has not been performed. The petitioner considered that such an assay was unnecessary since, given its high molecular weight, calcium lignosulphonate (40-65) is unlikely to enter the cells. The Panel agreed with this argument.

In a short-term 28-day toxicity study a No Observed Adverse Effect Level (NOAEL) of 1500 mg/kg bw/day was identified for calcium lignosulphonate (40-65) based on minimal focal/multifocal chronic inflammation in the rectum of male rats. In a 90-day subchronic toxicity study, the petitioner identified a NOAEL of 2000 mg/kg bw/day for calcium lignosulphonate (40-65), the highest dose tested. The Panel, however, considers this study inadequate for evaluating the safety of calcium lignosulphonate (40-65) due to the high incidence of lymphoid hyperplasia and lymphoid infiltration in the mandibular and mesenteric lymph nodes, in the Peyer’s patches and in the liver in all animals, including controls.

In a developmental toxicity study (21 days) in the rat, no treatment-related effects in dams or fetuses were reported up to the highest dose tested and a NOAEL of 1000 mg/kg bw/day can be identified for calcium lignosulphonate (40-65) from this study.

Exposure estimates were based on the reported European high percentile intakes of vitamins from food and Tolerable Upper Intake Levels (ULs) of vitamins for children and adults, and on the percentage of calcium lignosulphonate (40-65) proposed by the petitioner to be used as a carrier. The maximum intake of calcium lignosulphonate (40-65) resulting from its use as a carrier for vitamin A cannot be estimated for children under 10 years old and adults, as the food intake of this vitamin is higher than the UL. The maximum intake of calcium lignosulphonate (40-65) resulting from its use as a carrier for vitamin A varies between approximately 500 and 3700 µg/day for children aged 11-17 years. The maximum intake of calcium lignosulphonate (40-65) resulting from its use as a carrier for vitamin D ranges from approximately 2100 to 8000 µg/day for children under 18 years old and it is approximately 6500 µg/day for adults. The maximum intake of calcium lignosulphonate (40-65) resulting from its use as a carrier for vitamin E ranges from 88.8 to 224.3 mg/day for children under 18 years old and is 264 mg/day for adults. The maximum intake of calcium lignosulphonate (40-65) resulting from its use as a carrier for vitamin K is less than 200 mg/day.

The maximum intake of calcium lignosulphonate (40-65) resulting from its use as a carrier for multivitamins (vitamins A, D, E and K) ranges from 366.9 to 410.4 mg/day for children aged 11 to 17 years, ranges from 278.7 to 318.7 mg/day for children aged 3-10 years, is 265.3 mg/day for children under 3 years old, and is 439.3 mg/day for adults.

Exposure estimates of calcium lignosulphonate (40-65), resulting from its use as carrier for carotenoids as proposed by the petitioner, were based on the estimated intake of carotenoids from natural sources, food additives and food supplements. The estimated intakes of calcium lignosulphonate (40-65), resulting from its use as a carrier, ranges from less than 10 to over 100 mg/day for b-carotene and zeaxanthin, from less than 10 to 95 mg/day for lutein and from less than 10 to 125 mg/day for lycopene. No estimates have been made for intake of calcium lignosulphonate (40-65) resulting from its use as a carrier for canthaxanthin (food colour limited to saucisses de Strasbourg) and b-apo-8’carotenal (no intake data available and no uses as food supplement) as their intakes are likely to be low. The Panel cannot provide a more refined exposure assessment for calcium lignosulphonate (40-65) resulting from its use as carrier for these colours since these colours are still under evaluation in Europe and their intakes have not yet been evaluated.

The Panel considers that the available data on calcium lignosulphonate (40-65) were insufficient to establish an ADI.The Panel further considers that the 90-day study with a 4-week recovery period is inadequate for the evaluation of the safety of calcium lignosulphonate (40-65). Therefore, the Panel considers that long-term toxicity studies are needed to elucidate whether the histiocytosis in the mesenteric lymph nodes of the rats observed in the inadequate 90-day toxicity study may progress into a more adverse state with time.

Overall, based on the available information, the Panel concludes that the safety of use of calcium lignosulphonate (40-65), as a carrier for vitamins and carotenoids intended to be added to foods for colouring and nutrient purposes, cannot be assessed.